tag:theconversation.com,2011:/fr/topics/als-12070/articlesALS – The Conversation2023-05-30T12:23:06Ztag:theconversation.com,2011:article/2050962023-05-30T12:23:06Z2023-05-30T12:23:06ZAfter the ALS ice bucket challenge and the rise of MrBeast, stunt philanthropy might be here to stay<figure><img src="https://images.theconversation.com/files/527859/original/file-20230523-15345-lbuwlx.jpg?ixlib=rb-1.1.0&rect=59%2C623%2C4873%2C2670&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Jimmy Donaldson, aka MrBeast, leaned into charity to get a massive following.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/youtube-personality-jimmy-donaldson-better-known-as-mrbeast-news-photo/1247748364?adppopup=true">Michael Tran/AFP via Getty Images</a></span></figcaption></figure><p>Stunt philanthropy is what happens when influencers, other celebrities and people who aren’t famous at all use entertaining videos to encourage support for a charitable cause. </p>
<p>When their stunts go viral, it can lead to massive public engagement that raises lots of money and draws new attention to previously less visible causes. </p>
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<figcaption><span class="caption">Donald Trump took the ALS ice bucket challenge in 2014.</span></figcaption>
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<h2>Why stunt philanthropy matters</h2>
<p>The biggest early success with stunt philanthropy online was the <a href="https://www.usatoday.com/story/news/2017/07/03/ice-bucket-challenge-5-things-you-should-know/448006001/">ALS ice bucket challenge</a>. </p>
<p>People taking the challenge uploaded short videos in which someone dropped a bucket of icy water on their head. They then posted these clips on their social media accounts, tagging others to do the same and to donate to the ALS Association. Participants ranged from high school students to <a href="https://youtu.be/XS6ysDFTbLU">Bill Gates</a> and <a href="https://youtu.be/5W37Z6U16MY">Mark Zuckerberg</a>. Even <a href="https://youtu.be/oF3mmcYFoYs">Donald Trump</a> took the challenge, before his presidency. </p>
<p>The campaign raised <a href="https://www.als.org/stories-news/ice-bucket-challenge-dramatically-accelerated-fight-against-als">an estimated US$115 million</a> in 2014 for research tied to amyotrophic lateral sclerosis – a fatal neurological condition for which there is no cure. </p>
<p>More recently, stunt philanthropy has become associated with a single infuencer: Jimmy Donaldson. By late 2022, when he was 24 years old, the <a href="https://www.wnct.com/local-news/youtube-star-greenvilles-own-mrbeast-rethinks-old-notions-of-philanthropy/">entrepreneur who calls himself “MrBeast</a>” had <a href="https://www.guinnessworldrecords.com/news/2022/11/mr-beast-now-most-subscribed-youtuber-ever-overtaking-pewdiepie-726321">more followers on YouTube than anyone else, ever</a>.</p>
<p>Donaldson calls himself “<a href="https://viewpoint.pointloma.edu/the-rise-of-the-social-media-influencer/">YouTube’s biggest philanthropist</a>.” He has gained <a href="https://www.youtube.com/@MrBeast">more than 150 million YouTube subscribers</a> through his entertaining stunt videos, such as recreating a game show version of the <a href="https://youtu.be/0e3GPea1Tyg">popular Korean Netflix series “Squid Game</a>” and giving the winner $456,000.</p>
<p>He relies on <a href="https://observer.com/2023/02/mrbeasts-sponsors-can-reach-a-super-bowl-sized-audience-for-half-the-price-of-a-super-bowl-ad">corporate partners like Honey</a>, TikTok and Quidd to pull off the stunts that have made him a celebrity.</p>
<p>Donaldson’s stunt videos have helped him earn lots of money for himself through advertising and the <a href="https://www.nytimes.com/2021/05/04/technology/mr-beast-youtube.html">sale of socks, water bottles and other merchandise</a>. He has created his own candy company, <a href="https://feastables.com/">Feastables</a>, which he celebrated with a stunt video that featured his own replica of <a href="https://youtu.be/Hwybp38GnZw">Willy Wonka’s chocolate factory</a>.</p>
<p>He now runs a <a href="https://www.dexerto.com/entertainment/mrbeast-breaks-another-record-with-his-mrbeast-burger-restaurant-opening-1922897/">global burger chain that partners with local restaurants</a> and reportedly made <a href="https://www.forbes.com/sites/abrambrown/2022/01/14/the-highest-paid-youtube-stars-mrbeast-jake-paul-and-markiplier-score-massive-paydays/?sh=46f766d11aa7">$54 million in 2021</a> alone.</p>
<p>Building on his formula for creating viral content, Donaldson also creates stunt videos that raise awareness and money and amass needed goods for Ukrainian refugees, African orphans and a <a href="https://www.yahoo.com/entertainment/much-does-mrbeast-much-does-050300091.html">wide array of other causes</a>.</p>
<p>In addition to partnering with companies, Donaldson also teams up with nonprofits for his philanthropy-themed stunts. </p>
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<figcaption><span class="caption">In early 2023, Donaldson collaborated with SEE International to facilitate 1,000 cataract surgeries.</span></figcaption>
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<h2>Beast Philanthropy</h2>
<p>In May 2023, Donaldson worked with <a href="https://youtu.be/w1UzSiWUrr8">Hearing the Call</a> to provide hearing aids to 1,000 people across the U.S., Mexico, Guatemala, Brazil, South Africa, Malwai and Indonesia and donated $100,000 to organizations that promote education in sign language. The video his team made publicizing this campaign showcased the delighted looks on many of the faces of people getting the hearing aids.</p>
<p>Alongside posting these videos on his main YouTube channel, Donaldson has created a separate <a href="https://www.youtube.com/@BeastPhilanthropy">Beast Philanthropy</a> channel. Among the videos posted is one that celebrates <a href="https://youtu.be/STiUV6XXG4E">giving supplies to underfunded schools</a>, sponsored by Sun-Maid, a raisin producer, and another that showed <a href="https://youtu.be/BNO6DjteidM">homes being rebuilt in Kentucky following tornado devastation</a>, sponsored by Nord VPN, a tech company.</p>
<p>Some people have questioned <a href="https://www.thegamer.com/mrbeast-is-only-a-good-person-for-views/">Donaldson’s motives for his eye-catching charitable acts</a>, while others have raised ethical concerns about the way he <a href="https://www.deseret.com/entertainment/2023/2/2/23582916/mrbeast-backlash-1000-people-cataracts-surgery-blind-surgery">uses footage of people in need for online entertainment</a>.</p>
<p>It’s much easier for public displays of charitable giving to go viral today because of social media, but there are precedents from pre-internet days.</p>
<p>From 1966 to 2010, the entertainer <a href="https://www.oregonlive.com/tv/2015/09/what_happened_to_the_jerry_lew.html">Jerry Lewis</a> raised millions of dollars for the Muscular Dystrophy Association and spread awareness about the disease with help from his famous friends during annual 24-hour telethons. </p>
<p>And Lionel Richie and Michael Jackson convened a celebrity supergroup to perform the charity relief song “<a href="https://www.voanews.com/a/we-are-the-world-79429907/416483.html">We are the World</a>” in 1985 to raise money for African famine relief – following an example set by <a href="https://www.smoothradio.com/features/the-story-of/do-they-know-its-christmas-band-aid-lyrics-artists/">British musicians a year earlier</a>.</p>
<p>It’s hard to predict what the future holds for stunt philanthropy, but it seems to me that it’s probably here to stay. That is why I will continue to keep studying how <a href="https://scholar.google.com/citations?user=eFzpsScAAAAJ&hl=en&oi=ao">social media can influence charitable giving</a>.</p><img src="https://counter.theconversation.com/content/205096/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Monica Lea does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The person with the most YouTube followers calls himself ‘YouTube’s biggest philanthropist.’Monica Lea, PhD Student in Public Administration, University of Nebraska OmahaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2002102023-02-22T12:54:03Z2023-02-22T12:54:03ZHow frontotemporal dementia, the syndrome affecting Wendy Williams, changes the brain – research is untangling its genetic causes<figure><img src="https://images.theconversation.com/files/511473/original/file-20230221-16-3xvr3l.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1732%2C1732&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Some of the same genetic mutations can lead to FTD, ALS or symptoms of both.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/brain-lp-pr-royalty-free-illustration/1164761753">antoniokhr/iStock via Getty Images Plus</a></span></figcaption></figure><p>Around <a href="https://www.who.int/news-room/fact-sheets/detail/dementia">55 million people worldwide</a> suffer from dementia such as Alzheimer’s disease. On Feb. 22, 2024, it was revealed that former talk show host <a href="https://www.npr.org/2024/02/22/1233172648/wendy-williams-aphasia-frontotemporal-dementia-diagnosis">Wendy Williams</a> had been diagnosed with <a href="https://www.theaftd.org/what-is-ftd/disease-overview/">frontotemporal dementia, or FTD</a>, a rare type of dementia that typically affects people <a href="https://www.alzheimers.gov/alzheimers-dementias/frontotemporal-dementia">ages 45 to 64</a>. <a href="https://apnews.com/article/what-is-frontotemporal-dementia-bruce-willis-fbfdbfca4793bb65ef3f38f31e31bd68">Bruce Willis</a> is another celebrity who was diagnosed with the syndrome, according to his family. In contrast to Alzheimer’s, in which the major initial symptom is memory loss, FTD typically involves changes in behavior.</p>
<p>The <a href="https://www.nia.nih.gov/health/what-are-frontotemporal-disorders">initial symptoms of FTD</a> may include changes in personality, behavior and language production. For instance, some FTD patients exhibit inappropriate social behavior, impulsivity and loss of empathy. Others struggle to find words and to express themselves. This insidious disease can be especially hard for families and loved ones to deal with. There is no cure for FTD, and there are no effective treatments.</p>
<p><a href="https://www.theaftd.org/genetics-of-ftd/">Up to 40% of FTD cases</a> have some family history, which means a genetic cause may run in the family. Since researchers identified the first genetic mutations that cause FTD in 1998, <a href="https://doi.org/10.15252%2Fembj.201797568">more than a dozen genes</a> have been linked to the disease. These discoveries provide an entry point to determine the mechanisms that underlie the dysfunction of neurons and neural circuits in the brain and to use that knowledge to explore potential approaches to treatment.</p>
<p><a href="https://profiles.umassmed.edu/display/130139">I am a researcher</a> who studies the development of FTD and related disorders, including the motor neuron disease <a href="https://www.als.org">amyotrophic lateral sclerosis, or ALS</a>. ALS, also known as Lou Gehrig’s disease, results in progressive muscle weakness and death. Uncovering the similarities in pathology and genetics between FTD and ALS could lead to new ways to treat both diseases.</p>
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<figcaption><span class="caption">Wendy Williams’ care team announced her diagnosis of frontotemporal dementia on Feb. 22, 2024.</span></figcaption>
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<h2>Genetic causes of FTD</h2>
<p>Genes contain the instructions cells use to make the proteins that carry out functions essential to life. Mutated genes can result in mutated proteins that lose their normal function or become toxic. </p>
<p>How mutated proteins contribute to FTD has been under intense investigation for decades. For instance, one of the key proteins in FTD, called <a href="https://doi.org/10.1016%2Fj.neuron.2011.04.009">tau</a>, helps stabilize certain structures in neurons and can form clumps in diseased brains. Another key protein, <a href="https://doi.org/10.1038%2Fnrn.2017.36">progranulin</a>, regulates cell growth and a part of the cell called the lysosome that breaks down cellular waste products.</p>
<p>Remarkably, the most common genetic mutation in FTD – in a gene called C9orf72 – <a href="https://doi.org/10.15252%2Fembj.201797568">also causes ALS</a>. In fact, apart from the mutations in genes that encode for tau and progranulin, most genetic mutations that cause FTD <a href="https://doi.org/10.15252%2Fembj.201797568">also cause ALS</a>. Another protein, <a href="https://doi.org/10.15252/embj.201797568">TDP-43</a>, forms clumps in the brains of over 95% of ALS cases and almost half of FTD cases. Thus, these disorders share close links in genetics and pathology.</p>
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<figcaption><span class="caption">Frontotemporal dementia typically affects people under 60.</span></figcaption>
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<h2>Modifier genes</h2>
<p>The same genetic mutation can cause FTD in one patient, ALS in another or symptoms of both FTD and ALS at the same time. Remarkably, some people who carry these genetic mutations may have no obvious symptoms for decades.</p>
<p>One reason the same mutation can cause both FTD and ALS is that, in addition to <a href="https://theconversation.com/als-is-only-50-genetic-identifying-dna-regions-affected-by-lifestyle-and-environmental-risk-factors-could-help-pinpoint-avenues-for-treatment-179169">lifestyle and environmental factors</a>, other genes may also influence whether mutated genes lead to disease. Identifying these <a href="https://doi.org/10.1016%2Fj.neuron.2020.08.022">modifier genes</a> in FTD, ALS and other neurodegenerative diseases could lead to new treatment approaches by boosting the activity of those that protect against disease or suppressing the activity of those that promote disease. </p>
<p>Modifier genes have long been a focus of research in <a href="https://www.umassmed.edu/fen-biaogaolab/">my laboratory</a> at the University of Massachusetts Chan Medical School. When my laboratory was still in San Francisco, we collaborated with neurologist <a href="https://profiles.ucsf.edu/bruce.miller">Bruce Miller</a> and generated the first stem cell lines from FTD patients with mutations in <a href="https://doi.org/10.1016%2Fj.celrep.2012.09.007">progranulin</a> and <a href="https://doi.org/10.1007%2Fs00401-013-1149-y">C9orf72</a>. These stem cells can be turned into neurons for researchers to study in a petri dish. My team also uses fruit flies to identify modifier genes and then test how they influence disease in neurons from patients with FTD or ALS.</p>
<p>For instance, in close collaboration with cell biologist <a href="https://www.stjude.org/directory/t/j-paul-taylor.html">J. Paul Taylor</a>, my laboratory was among the first to discover a small <a href="https://doi.org/10.1038%2Fnature14974">subset of modifier genes</a> that help transport molecules into or out of the nucleus of a neuron. We also <a href="https://doi.org/10.1016%2Fj.neuron.2016.09.015">discovered</a> <a href="https://doi.org/10.1073%2Fpnas.1901313116">modifier genes</a> that encode for some proteins that help repair damaged DNA. Targeting these modifier genes using <a href="https://doi.org/10.1089%2Fnat.2018.0725">gene-silencing techniques</a> developed by Nobel laureate <a href="https://www.nobelprize.org/prizes/medicine/2006/mello/facts/">Craig Mello</a> and other researchers at UMass Chan could offer potential treatments.</p>
<h2>Treating behavioral changes in FTD</h2>
<p>Because the brain is an extremely complex organ, it can be very difficult to understand what causes personality and behavioral changes in FTD patients. </p>
<p>Over the years, my team has used mice to study the causes of these changes. For instance, we found that the reduced social interaction we observed in mice engineered to have FTD is linked to <a href="https://doi.org/10.1038%2Fnm.3717">two different</a> <a href="https://doi.org/10.1038%2Fs41593-019-0397-0">disease proteins</a> in the same part of the brain, suggesting that this symptom may be caused by defects in the same neural circuit. These deficits could be reversed by injecting a molecule called <a href="https://doi.org/10.1038%2Fnm.3717">microRNA-124</a> into the prefrontal cortex, the part of the brain that controls social behaviors.</p>
<p>Moreover, with my longtime collaborator neuroscientist <a href="https://www.upstate.edu/psych/faculty.php?empID=yaow">Wei-Dong Yao</a>, our labs found that mice with FTD have <a href="https://doi.org/10.1038%2Fnm.3717">defects at</a> <a href="https://doi.org/10.1038%2Fs41593-019-0397-0">the synapses</a> in this part of the brain. Synapses are areas where neurons are in contact with each other and play an important role in transporting information in the nervous system. Recently, he found that <a href="https://doi.org/10.1016/j.neuron.2022.12.027">lack of empathy</a> in another mouse model of FTD could be reversed by increasing activity in the prefrontal cortex. </p>
<p>Further research to understand the molecular mechanisms and brain circuitry behind FTD offer hope that its devastating symptoms, including behavioral and personality changes, will be treatable in the future.</p>
<p><em>This is an updated version of an article originally published on Feb. 22, 2023.</em></p><img src="https://counter.theconversation.com/content/200210/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Fen-Biao Gao receives and has previously received funding from the NIH, The Muscular Dystrophy Association, The Association for FTD, Target ALS Foundation, The ALS Association, The Tau Consortium, The Consortium for Frontotemporal Dementia Research, The Ricico Fund, The Cellucci Fund, Merck, and Stealth BioTherapeutics.
He works for the NIH as a member of its CMND study section, for The Muscular Dystrophy Association as a member of its Research Advisory Council and for The Association for FTD as a member of its Scientific Review Panel. </span></em></p>FTD leads to changes in personality and behavior. Understanding its genetic and molecular causes could lead to new ways to treat neurodegenerative diseases.Fen-Biao Gao, Professor of RNA Therapeutics, Governor Paul Cellucci Chair in Neuroscience Research, Founding Director of Frontotempral Dementia Research Center, UMass Chan Medical SchoolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1819542022-05-27T03:07:52Z2022-05-27T03:07:52ZOn your back? Side? Face-down? Mice show how we sleep may trigger or protect our brain from diseases like ALS<figure><img src="https://images.theconversation.com/files/462143/original/file-20220510-18-s2q22z.jpg?ixlib=rb-1.1.0&rect=35%2C35%2C5955%2C3952&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://images.unsplash.com/photo-1531353826977-0941b4779a1c?ixlib=rb-1.2.1&ixid=MnwxMjA3fDB8MHxwaG90by1wYWdlfHx8fGVufDB8fHx8&auto=format&fit=crop&w=3270&q=80">Unsplash/Lux Graves</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is the <a href="http://dx.doi.org/10.1136/jnnp.61.2.131">most common form</a> of motor neuron disease. People with ALS progressively lose the ability to initiate and control muscle movements, including the ability to speak, swallow and breathe. </p>
<p>There is no known cure. But recently, <a href="https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-022-00291-4">we studied mice</a> and identified a new target in the fight against this devastating disease: the brain’s waste clearance system. </p>
<p><a href="https://www.nature.com/articles/s41593-018-0235-9">Neurodegenerative diseases</a> – including Parkinson’s disease, Alzheimer’s and multiple sclerosis – share many similarities, even though their clinical symptoms and disease progression may look very different. The incidence of these diseases increase with age. They are progressive and relentless, and result in gradual loss of brain tissue. We also see waste proteins accumulate in the brain. </p>
<p>Our new research looked at how the glymphatic system, which removes waste from the brain, could prevent ALS.</p>
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<em>
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Read more:
<a href="https://theconversation.com/als-is-only-50-genetic-identifying-dna-regions-affected-by-lifestyle-and-environmental-risk-factors-could-help-pinpoint-avenues-for-treatment-179169">ALS is only 50% genetic – identifying DNA regions affected by lifestyle and environmental risk factors could help pinpoint avenues for treatment</a>
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<h2>Protein chains, folds and misfolds</h2>
<p>Inside our bodies, long protein chains fold to form functional shapes that allow them to perform <a href="https://medlineplus.gov/genetics/understanding/howgeneswork/protein/">specific tasks</a> like creating antibodies to fight off infection, supporting cells or transporting molecules. </p>
<p>Sometimes this process goes awry, resulting in “misfolded” proteins that clump together to form aggregates. Misfolded protein can grow and fragment, creating seeds that spread throughout the brain to form new clusters.</p>
<p>The accumulation of waste proteins begins early in the neurodegenerative disease process – well before the onset of symptoms and brain loss. As researchers, we wanted to see if eliminating or slowing the spread of these waste proteins and their seeds could halt or slow the progression of disease.</p>
<h2>Targeting waste removal</h2>
<p>The <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636982/">glymphatic system</a> removes waste, including toxic proteins, from the brain. </p>
<p>This brain-wide network of fluid-filled spaces, known as <a href="https://fluidsbarrierscns.biomedcentral.com/articles/10.1186/s12987-015-0010-1">Virchow-Robin spaces</a>, is mostly switched off while we’re awake. But it kicks into gear during sleep to distribute compounds essential to brain function and to get rid of toxic waste. </p>
<p>This may explain why <a href="https://theconversation.com/animals-sleep-but-little-is-known-about-how-sharks-do-it-180219">all creatures</a>, great and small (<a href="https://qbi.uq.edu.au/article/2013/08/flies-sleep-just-us">even flies</a>), need sleep to survive. (Interestingly, whales and dolphins alternate their sleep between brain hemispheres, keeping the other hemisphere awake to watch for predators and alerting them to breathe!)</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/462145/original/file-20220510-17-ip9qf6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="pair of dolphins underwater" src="https://images.theconversation.com/files/462145/original/file-20220510-17-ip9qf6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/462145/original/file-20220510-17-ip9qf6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/462145/original/file-20220510-17-ip9qf6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/462145/original/file-20220510-17-ip9qf6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/462145/original/file-20220510-17-ip9qf6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/462145/original/file-20220510-17-ip9qf6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/462145/original/file-20220510-17-ip9qf6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Unlike us, dolphins sleep with one side of their brain at a time.</span>
<span class="attribution"><a class="source" href="https://images.unsplash.com/photo-1562742686-0b38a29473ab?ixlib=rb-1.2.1&ixid=MnwxMjA3fDB8MHxwaG90by1wYWdlfHx8fGVufDB8fHx8&auto=format&fit=crop&w=3273&q=80">Unsplash/NOAA</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>As we age, sleep quality <a href="https://doi.org/10.1111/j.1532-5415.2008.01755.x">declines</a> and the risk of neurodegenerative disease, including ALS, increases. </p>
<p>Sleep disturbances are also a common symptom of ALS and research has shown a single night without sleep can result in <a href="https://www.pnas.org/doi/10.1073/pnas.1721694115">increased accumulation</a> of toxic waste protein in the brain. As such, we thought glymphatic function might be impaired in ALS. </p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/longer-naps-in-the-day-may-be-an-early-sign-of-dementia-in-older-adults-179365">Longer naps in the day may be an early sign of dementia in older adults</a>
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<h2>Ageing mice</h2>
<p>To investigate this, we looked to mice. The animals were genetically modified to express human TDP-43 – the protein implicated in ALS. By feeding these mice food containing an antibiotic (doxycycline), we were able to turn the TDP-43 protein expression off and they aged normally. But when the mice are switched to normal food, TDP-43 expression is turned on and misfolded proteins begin to accumulate. </p>
<p>Over time, the mice display the classical signs of ALS including progressive muscle impairments and brain atrophy. </p>
<p>Using magnetic resonance imaging (MRI) to see brain structure, we investigated glymphatic function in these mice just three weeks after turning on TDP-43 expression.</p>
<p>As we watched the glymphatic system go to work, we saw the TDP-43 mice had worse glymphatic clearance than the control mice that had not been genetically modified. Importantly, these differences were seen very early in the disease process. </p>
<p>Our study provides the first evidence the glymphatic system might be a potential therapeutic target in the treatment of ALS.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1508474747537039367"}"></div></p>
<h2>How can we improve glymphatic function?</h2>
<p>Not all sleep is equal. Sleep includes both rapid eye movement (REM) and non-REM sleep. This latter stage includes slow wave sleep – <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309589/">when the glymphatic system is most active</a>. Sleep therapies that enhance this phase may prove to be particularly beneficial for preventing diseases like ALS. </p>
<p>Sleep position is also thought to affect glymphatic clearance. </p>
<p>Research conducted in rodents has <a href="https://pubmed.ncbi.nlm.nih.gov/26245965/">demonstrated</a> glymphatic clearance is most efficient in the lateral (or side-sleeping) position, compared to either supine (on the back) or prone (front-lying) positions. The reasons for this are not yet fully understood but possibly relates to the effects of gravity, compression and stretching of tissue.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/sleeping-on-it-helps-you-better-manage-your-emotions-and-mental-health-heres-why-179156">‘Sleeping on it’ helps you better manage your emotions and mental health – here’s why</a>
</strong>
</em>
</p>
<hr>
<p>Lifestyle choices may be helpful in improving glymphatic function too. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747747/">Omega-3</a>, found in marine-based fish, has long been considered to be beneficial to health and reduced risk of neurodegenerative diseases. New research shows these benefits may be partly due to the positive effect of <a href="https://pubmed.ncbi.nlm.nih.gov/27789520/">Omega-3 on glymphatic function</a>.</p>
<p>Moderate consumption of alcohol has been shown to improve waste clearance. In mouse studies, both short and long-term exposure to <a href="https://pubmed.ncbi.nlm.nih.gov/29396480/">small amounts of alcohol were shown to boost glymphatic function</a> while high doses had the opposite effect. </p>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/28579942/">Exercise</a> has also been shown to be beneficial. </p>
<p>All these studies show small lifestyle changes can improve brain waste clearance to minimise the risk of neurodegenerative disease. Next, research needs to focus on therapies directly targeting the glymphatic system to help those already suffering from these debilitating diseases.</p><img src="https://counter.theconversation.com/content/181954/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Wright receives funding from the NHMRC and FightMND. He has previously received funding from the Bethlehem Griffiths Research Foundation to investigate glymphatic function in ALS.</span></em></p>Our new research with mice visualised how differently aged brains pump out toxic protein waste during sleep.David Wright, Associate Professor of Medical Imaging, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1791692022-04-13T12:13:53Z2022-04-13T12:13:53ZALS is only 50% genetic – identifying DNA regions affected by lifestyle and environmental risk factors could help pinpoint avenues for treatment<figure><img src="https://images.theconversation.com/files/456422/original/file-20220405-14-ks7fbg.png?ixlib=rb-1.1.0&rect=0%2C0%2C2309%2C1299&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Epigenetics is how behavior and environment affect gene expression.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/the-dna-spiral-royalty-free-image/1293534045">Iryna Dobytchina/iStock via Getty Images Plus</a></span></figcaption></figure><p><a href="https://medlineplus.gov/amyotrophiclateralsclerosis.html">Amyotrophic lateral sclerosis</a> is a devastating neurodegenerative disease that affects about <a href="https://dx.doi.org/10.1038%2Fncomms12408">1 in 50,000 people</a>. Well-known people who suffered from ALS include baseball player <a href="https://www.als.org/understanding-als/lou-gehrig">Lou Gehrig</a>, who lived two years after he was diagnosed, and scientist <a href="https://www.nbcnews.com/health/health-care/stephen-hawking-had-als-55-years-how-did-he-do-n857006">Stephen Hawking</a>, who lived for an extraordinary 55 years after his diagnosis. While the severity and speed of disease progression <a href="https://www.als.org/understanding-als">vary from person to person</a>, most people with ALS die within two to five years after diagnosis. <a href="https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Amyotrophic-Lateral-Sclerosis-ALS-Fact-Sheet">No effective therapy</a> currently exists.</p>
<p>Little is known about what causes or increases someone’s risk of developing ALS. Researchers think it’s only <a href="https://doi.org/10.1001/jamaneurol.2019.2044">around 50% genetic</a>, indicating that there are strong environmental and lifestyle risk factors affecting disease development. But very few of these risk factors have been identified.</p>
<p><a href="https://www.researchgate.net/profile/Ramona-Zwamborn-2">We</a> <a href="https://www.researchgate.net/profile/Paul-Hop-2">are</a> <a href="https://www.researchgate.net/scientific-contributions/Jan-H-Veldink-39091027">a</a> team of <a href="https://www.projectmine.com/country/the-nederlands/">neuroscientists</a> with a special interest in <a href="https://medlineplus.gov/genetics/understanding/howgeneswork/epigenome/">epigenetics</a>, the study of how the environment influences DNA. By examining the epigenetics of ALS, we found that differences in metabolism, cholesterol and immunity may play a role in disease progression.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/xrIjFVMliOQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">ALS involves the progressive degeneration of the neurons involved in muscle movement.</span></figcaption>
</figure>
<h2>Nongenetic risk factors</h2>
<p>Epigenetics opens a window into the role environmental factors play in genetic diseases like ALS. One common type of epigenetic mechanism is <a href="https://doi.org/10.1007/978-1-61779-612-8_23">DNA methylation</a>, an on-off switch for certain regions of DNA that shift throughout a person’s lifetime. The ways these on-off patterns change are known to be shaped by environmental and lifestyle factors.</p>
<p>To unravel how DNA methylation affects ALS, we analyzed DNA samples and lifestyle questionnaire responses from almost 10,000 patients with and without ALS. This data was collected by <a href="https://www.projectmine.com/">Project MinE</a>, an international initiative creating a database of the genetic profiles of ALS patients. </p>
<p>We discovered <a href="http://dx.doi.org/10.1126/scitranslmed.abj0264">differences in methylation</a> patterns between people with ALS and people without ALS in 45 DNA regions. When we examined the specific genes located in these areas, we found that people with ALS mainly showed differences in methylation on genes that play a role in metabolism, cholesterol production and immunity. These findings support a recent <a href="https://doi.org/10.1038/s41588-021-00973-1">Project MinE study</a> that showed a causal link between high cholesterol levels and ALS.</p>
<p>Our team also examined DNA methylation patterns that reflect exposure to certain environmental or lifestyle factors (such as smoking or high body mass index), or biological processes (such as aging). Even after controlling for the effects of these other common risk factors, we found that metabolism, cholesterol and immunity were still associated with ALS.</p>
<p>Changes in methylation patterns for multiple DNA regions, and especially those related to immune processes, were also associated with survival rates for people living with ALS.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/456406/original/file-20220405-14-p1qj70.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of DNA methylation and histone modification" src="https://images.theconversation.com/files/456406/original/file-20220405-14-p1qj70.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/456406/original/file-20220405-14-p1qj70.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=408&fit=crop&dpr=1 600w, https://images.theconversation.com/files/456406/original/file-20220405-14-p1qj70.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=408&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/456406/original/file-20220405-14-p1qj70.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=408&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/456406/original/file-20220405-14-p1qj70.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=513&fit=crop&dpr=1 754w, https://images.theconversation.com/files/456406/original/file-20220405-14-p1qj70.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=513&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/456406/original/file-20220405-14-p1qj70.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=513&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Environmental factors can affect genetic material through an epigenetic mechanism that involves methyl groups tagging DNA to turn it on or off.</span>
<span class="attribution"><a class="source" href="http://commonfund.nih.gov/epigenomics/figure">National Institutes of Health</a></span>
</figcaption>
</figure>
<h2>Next steps</h2>
<p>Currently, no cure exists for this devastating and deadly disease. Our study helps clarify the biological processes that underlie ALS risk factors and disease progression, and could potentially be used to develop new treatments or preventive interventions.</p>
<p>It is important to emphasize, however, that the epigenetic differences between people with and without ALS that we found were small. Our study also doesn’t prove that changes in genes involved in metabolism, cholesterol production or immunity cause or are influenced by ALS. More research is needed before physicians can confidently recommend lifestyle changes to help cut the risk of ALS.</p>
<p>[<em>Get fascinating science, health and technology news.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-fascinating">Sign up for The Conversation’s weekly science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/179169/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jan Veldink receives funding from the European Research Council (ERC) and Biogen (sponsored research agreements).</span></em></p><p class="fine-print"><em><span>Paul J. Hop and Ramona Zwamborn do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Genetic modifications to DNA regions involved in metabolism, cholesterol and immunity may play a role in ALS disease progression.Ramona Zwamborn, PhD candidate in Neurogenetics, Utrecht UniversityJan Veldink, Professor of Neurology and Neurogenetics, Utrecht UniversityPaul J. Hop, PhD candidate in Neurogenetics, Utrecht UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1632102021-06-24T18:17:22Z2021-06-24T18:17:22ZResearch that shines light on how cells recover from threats may lead to new insights into Alzheimer’s and ALS<figure><img src="https://images.theconversation.com/files/408024/original/file-20210623-27-1ckyw2a.png?ixlib=rb-1.1.0&rect=6%2C3%2C1147%2C1097&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Ubiquitin tags in cells serve different functions depending on stress conditions.</span> <span class="attribution"><span class="source">Michael Hughes</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>Our bodies contain a special protein tag that plays a role in how cells recover from specific threats to their survival, according to new research I co-authored. Understanding how this process works may be key to future treatments for neurodegenerative diseases, such as Alzheimer’s disease and some forms of dementia.</p>
<p>Cells regularly encounter potentially harmful changes in their environment, such as fluctuating temperature or exposure to UV light or toxins. To ensure survival, cells have evolved complex ways to adapt to these stressful changes. These mechanisms range from temporary changes in metabolism to wholesale shutdown of critical biological processes that might otherwise be permanently damaged. </p>
<p>For example, many cellular stresses temporarily shut down protein production while <a href="https://www.nature.com/scitable/definition/mrna-messenger-rna-160/">messenger RNAs</a>, which carry part of the DNA code through the cell, become sequestered in dense structures known as <a href="https://doi.org/10.1016/j.cell.2020.03.046">stress granules</a>. When the stress passes, the stress granules are disassembled and cells emerge from this defensive state to resume normal activities. </p>
<p>But until now, molecular biologists <a href="https://scholar.google.com/citations?user=n1F7nY8AAAAJ&hl=en&oi=sra">like me</a> didn’t understand exactly how this mechanism worked. </p>
<p>In a pair of peer-reviewed studies published in the journal Science on June 25, 2021, my colleagues and I working in <a href="https://scholar.google.com/citations?user=D8NsvBIAAAAJ&hl=en&oi=ao">J. Paul Taylor</a>’s cell and molecular biology lab explain how a protein known as <a href="https://www.healthline.com/health/ubiquitin#where-its-found">ubiquitin</a> is responsible for getting cells back up and running once the coast is clear.</p>
<p><a href="https://science.sciencemag.org/content/372/6549/eabc3593/tab-article-info">In the first study</a>, I discovered that different types of stress lead to specific proteins in cells getting tagged with ubiquitin in distinct ways. I exposed cells to either heat stress or a toxic chemical, then blocked the ubiquitin-tagging process after seemingly identical stress granules formed. To my surprise, blocking ubiquitin tagging only prevented stress granule disassembly for heat shock. Importantly, I also found that cells were unable to restart key biological processes like protein production and transport when these stress granules remained present, even after a return to normal temperatures.</p>
<p><a href="https://science.sciencemag.org/content/372/6549/eabf6548/tab-article-info">In the second study</a>, my colleague <a href="https://scholar.google.com/citations?user=hUDqV14AAAAJ&hl=en">Youngdae Gwon</a> looked closer into this process. He discovered that heat stress triggers ubiquitin tagging of a key protein that allows an enzyme to disassemble stress granules. This enzyme grabs onto the ubiquitin tag and uses it as a handle to pull the structure apart.</p>
<h2>Why it matters</h2>
<p>Researchers have linked stress granule biology and the stress response process in general to <a href="https://doi.org/10.1126/science.abb8032">several neurodegenerative diseases</a>, including Alzheimer’s disease, ALS or Lou Gehrig’s disease, and some forms of dementia. </p>
<p>For example, mutations in the the same protein, which we found to be necessary to dissemble stress granules, can cause inherited neurodegenerative diseases. Understanding how stress granules are regulated is critical to getting a better grasp on how these diseases work and potentially finding new treatments for them. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/piBTwMdXjBQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Stress granules play a role in the development of neurodegenerative diseases like ALS.</span></figcaption>
</figure>
<h2>What still isn’t known</h2>
<p>Although we identified several key factors in the role ubiquitin plays in the disassembly of stress granules, many molecular details of this process remain unknown. To gain further insight, scientists will need to identify which enzymes are responsible for putting the ubiquitin tag on proteins during stress in the first place. Additionally, it will be important to understand how mutations that lead to neurodegenerative diseases might also affect the stress recovery process.</p>
<h2>What other research is being done</h2>
<p>Researchers are investigating various aspects of stress granule biology and its links to neurodegenerative disease. Some are working to <a href="https://doi.org/10.1083/jcb.202009079">recreate stress granules in a test tube</a> to explore questions not easily answered by working in cells. And others are looking inside live neurons, mice and fruit flies to understand how disease mutations affect stress recovery in living cells and creatures.</p>
<p>[<em><a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-corona-important">The Conversation’s most important coronavirus headlines, weekly in a science newsletter</a></em>]</p><img src="https://counter.theconversation.com/content/163210/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Brian Andrew Maxwell receives funding from NIH and the St. Jude George Mitchell Fellowship </span></em></p>Insight on how a unique protein plays a role in cellular stress responses may provide more clues on how to treat diseases like ALS and Alzheimer’s.Brian Andrew Maxwell, Scientist in Cell Biology, St. Jude Children’s Research Hospital Graduate School of Biomedical SciencesLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1423402020-07-20T19:51:11Z2020-07-20T19:51:11ZALS scientific breakthrough: Diabetes drug metformin shows promise in mouse study for a common type of ALS<figure><img src="https://images.theconversation.com/files/348256/original/file-20200719-31-apeztc.jpg?ixlib=rb-1.1.0&rect=1%2C2%2C555%2C437&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A man with ALS uses a head-mounted laser pointer to communicate with his wife, by pointing to letters and words on a communication board.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Using_a_head_mounted_laser_to_point_to_a_communication_board.jpg">Fezcat via Wikipedia.com</a></span></figcaption></figure><p>An FDA-approved diabetes drug shows early signs of promise against the most common genetic form of amyotrophic lateral sclerosis, a devastating neurological condition that causes paralysis. </p>
<p>ALS is a <a href="http://doi.org/10.1056/NEJMra1603471">progressive disease that affects neurons in the brain and spinal cord</a>. Motor neurons transmit signals from our brain to our muscles and allow us to move. ALS causes these motor neurons to die, resulting in the loss of a patient’s ability to speak, eat, move and breathe. Notable ALS patients include New York Yankees baseball star Lou Gehrig (the disease is often called Lou Gehrig’s disease), physicist Stephen Hawking and New Orleans Saints football star Steve Gleason. There are currently <a href="https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/als/conditions/als_amyotrophic_lateral_sclerosis.html">more than 30,000 cases of ALS in the United States</a>, and life expectancy after diagnosis is typically 2 to 5 years. There is currently <a href="http://doi.org/10.1056/NEJMra1603471">no cure for ALS</a>. </p>
<p><a href="https://neurogenetics.med.ufl.edu/faculty/dr-laura-p-w-ranum/">I am a scientist</a> who studies neurological diseases that run in families, and I have been working hard to find a treatment to stop ALS. Our team has made a discovery, <a href="https://www.pnas.org/cgi/doi/10.1073/pnas.2005748117">detailed in a scientific study</a> and highlighted in <a href="https://doi.org/10.1073/pnas.2012363117">a commentary by Nobel Prize winner Michael Rosbash</a>, that paves the way for further research for improving disease in a genetic type of ALS caused by <a href="http://doi.org/10.1016/j.neuron.2011.09.011">a mutation in a gene</a> <a href="https://doi.org/10.1016/j.neuron.2011.09.010">with the unwieldy name</a> <em>chromosome 9 open reading frame 72 (C9orf72)</em>, based on its location on chromosome 9. In addition to ALS, mutations in this gene can also cause frontotemporal dementia, which can cause apathy, loss of emotional control and cognitive decline. Some patients with the <a href="https://doi.org/10.3389/fnins.2020.00042">C9orf72 mutation develop ALS, others develop frontotemporal dementia and some develop both</a>. Together, these diseases are referred to here as C9-ALS/FTD. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/348257/original/file-20200719-31-16upzky.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/348257/original/file-20200719-31-16upzky.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=421&fit=crop&dpr=1 600w, https://images.theconversation.com/files/348257/original/file-20200719-31-16upzky.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=421&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/348257/original/file-20200719-31-16upzky.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=421&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/348257/original/file-20200719-31-16upzky.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=529&fit=crop&dpr=1 754w, https://images.theconversation.com/files/348257/original/file-20200719-31-16upzky.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=529&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/348257/original/file-20200719-31-16upzky.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=529&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">When motor neurons are damaged and die, muscles atrophy and patients lose the ability to speak, eat, move and breathe.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/amyotrophic-lateral-sclerosis-concept-royalty-free-illustration/997071088?adppopup=true">blueringmedia / Getty Images</a></span>
</figcaption>
</figure>
<h2>Repeating theme in ALS and other neurodegenerative diseases</h2>
<p>I have been focusing on C9-ALS, which is the most common genetic type of ALS which is caused by a <a href="http://doi.org/10.1016/j.neuron.2011.09.011">mutation in the C9orf72</a> <a href="https://doi.org/10.1016/j.neuron.2011.09.010">gene</a>. The mutation occurs when six letters of DNA that make up part of the gene’s genetic code – GGGGCC – are repeated hundreds of extra times. It is as if a single word is repeated hundreds of times in the same sentence.</p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>The gene mutation that causes C9-ALS is part of a much larger family of diseases that are caused by similar expansions of short repeated segments of DNA. </p>
<p>Repeat expansion mutations were first discovered in 1991 as the cause of Fragile X syndrome and spinal bulbar muscular atrophy, and this type of mutation is now <a href="http://doi.org/10.1016/j.neuron.2013.02.022">known to cause more than 50</a> <a href="http://doi.org/10.3390/ijms20133365">different neurologic diseases</a>. </p>
<p>Over the past 30 years, I have been studying these types of expansion mutations, including those that cause a disease called spinocerebellar ataxia type 8 <a href="https://doi.org/10.1038/7710">that affects coordination</a> and the <a href="http://doi.org/10.1126/science.1062125">muscle disease myotonic dystrophy type 2</a>. I have been particularly interested in understanding how these gene mutations work, and there have been some big surprises. </p>
<h2>One mutation, two RNAs and six unexpected proteins</h2>
<p>Typically, a gene encoded in DNA makes a single copy of an intermediate molecule called RNA, which the cell uses to manufacture a protein. Also, portions of genes are typically not expressed as proteins. The repeat expansion mutation in C9-ALS and many other neurological diseases occurs in these gene regions not expected to produce proteins. But, when a repeat expansion is present, the mutated region <a href="http://doi.org/10.1146/annurev-neuro-070918-050405">produces up to six unexpected and toxic proteins</a>. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/348260/original/file-20200719-21-dxf9pr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/348260/original/file-20200719-21-dxf9pr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/348260/original/file-20200719-21-dxf9pr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=529&fit=crop&dpr=1 600w, https://images.theconversation.com/files/348260/original/file-20200719-21-dxf9pr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=529&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/348260/original/file-20200719-21-dxf9pr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=529&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/348260/original/file-20200719-21-dxf9pr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=664&fit=crop&dpr=1 754w, https://images.theconversation.com/files/348260/original/file-20200719-21-dxf9pr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=664&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/348260/original/file-20200719-21-dxf9pr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=664&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This expansion mutation was previously thought to be silent and not produce any proteins. Now we know it produces two RNAs and six RAN proteins.</span>
<span class="attribution"><span class="source">Laura Ranum</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>In 2006, we started to unravel how this happens by discovering that the spinocerebellar ataxia type 8 repeat expansion mutation produces <a href="https://doi.org/10.1038/ng1827">two RNAs instead of just one</a>. This <a href="https://doi.org/10.1016/j.molcel.2005.09.002">double-the-trouble scenario</a> was also found in myotonic dystrophy type 1 and is now known to occur for <a href="https://doi.org/10.1146/annurev-neuro-070918-050405">many repeat expansion disorders</a>. </p>
<p>In 2011, we discovered that these repeat-expansion mutations also break the previously established dogma that a start signal embedded in the genetic code is required to make proteins. In contrast, we showed that when a repeat expansion mutation is present, proteins are produced without a start signal and extra, unexpected proteins are made – <a href="https://doi.org/10.1073/pnas.1013343108">up to six for each expansion mutation</a>. </p>
<p>We called these rogue proteins <a href="https://doi.org/10.1073/pnas.1013343108">repeat associated non-AUG (RAN) proteins</a>. These proteins accumulate in neurons and other brain cells, damaging them and causing disease. RAN proteins have now been found in 10 different repeat expansion diseases, including <a href="http://doi.org/10.1146/annurev-neuro-070918-050405">Huntington’s disease and Fragile X tremor ataxia syndrome</a>.</p>
<p>In C9-ALS mice, we have shown that <a href="http://doi.org/10.1016/j.neuron.2019.11.007">destroying RAN proteins using antibodies in mice</a> improves lifespan, the survival of motor neurons and other key aspects of the disease. </p>
<p>In the newly published study in the Proceedings of the National Academy of Sciences, our team discovered a cellular switch that, when turned on, hijacks the cell and forces it into making RAN proteins. <a href="https://www.pnas.org/cgi/doi/10.1073/pnas.2005748117">RNA copies of the expansion mutations turn on this switch</a>, called the protein kinase R pathway. </p>
<p>Turning off the protein kinase R pathway switch blocks RAN protein production for multiple types of disease-causing repeat expansions, making protein kinase R a possible Achilles heel for RAN protein diseases. These results had me and my colleague <a href="https://neurogenetics.med.ufl.edu/faculty/tao-zu/">Tao Zu</a>, a research assistant professor, tremendously excited. </p>
<h2>Metformin shows promise for C9-ALS/FTD and other expansion diseases</h2>
<p>I decided that we should test the FDA-approved diabetes drug metformin after hearing <a href="https://www.mcgill.ca/biochemistry/about-us/department/faculty-members/sonenberg">Nahum Sonenberg</a>, a longtime collaborator, present data showing that this drug improved disease in mice with Fragile X syndrome, <a href="http://doi.org/10.1038/nm.4335">a disease involving a missing protein</a>. Even though Fragile X disrupts protein production in a completely different way, I thought that because metformin normalized protein production in Fragile X syndrome, maybe it could do the same for RAN protein diseases.</p>
<p>Although it was a long shot, I asked Dr. Zu to test metformin in cells to see if the drug would lower RAN protein levels. The results in cells very clearly showed that it did. We went on to <a href="https://www.pnas.org/cgi/doi/10.1073/pnas.2005748117">show that metformin inhibits protein kinase R, reduces RAN proteins and improves disease in C9-ALS/FTD mice</a>. It is important to emphasize that this approach is thought to work for this particular genetic form of ALS and frontotemporal dementia because the <em>C9orf72</em> mutation makes RAN proteins. In a previous research study conducted by a different group, metformin treatment was <a href="https://doi.org/10.1371/journal.pone.0024189">not effective in mice with a different form of ALS that does not produce RAN proteins</a>. </p>
<p>Typically, it takes a decade or more to move promising research from the lab to the clinic. Metformin was introduced in 1957 in France and approved in 1995 in the United States. Because metformin is widely used as a <a href="https://doi.org/10.2147/DDDT.S141675">safe and effective treatment for Type 2 diabetes</a> with few side effects, we can skip the arduous drug-development process and immediately test if the benefits of metformin treatment in mice are also found in people with C9-ALS. </p>
<p>My colleagues and I at the University of Florida have already <a href="https://clinicaltrials.gov/ct2/show/NCT04220021">started a Phase 2 open-label trial</a> to test the effects of metformin in C9-ALS patients. In this first open-label trial, in which everyone will receive the drug, we will be testing to see if the drug is safe for patients with C9-ALS and if it lowers RAN protein levels in the cerebrospinal fluid. </p>
<p>If the results are promising, the next step would be to test the potential benefits of the drug in a larger, placebo-controlled trial. We are especially excited about metformin as a potential treatment for C9-ALS/FTD and other repeat expansion disorders, because by reducing RAN proteins, it could address a fundamental problem common to many of these diseases.</p><img src="https://counter.theconversation.com/content/142340/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr. Laura Ranum has received research funding from the National Institutes of Health (RO1 NS098819, R37NS040389 and PO1-NS058901), the Department of Defense (W81XWH1910654), Target ALS, ALS Association, Muscular Dystrophy Association, Myotonic Dystrophy Foundation, National Ataxia Foundation and Packard Center. She is an inventor on patents on RAN translation and is a co-founder of RanTran Inc. and has served as a scientific advisor to Biogen. She is a full time employee of the University of Florida, where she directs the Center for NeuroGenetics and is the Kitzman Family Professor in the Department of Molecular Genetics and Microbiology in the College of Medicine at the University of Florida.
</span></em></p>Amyotrophic lateral sclerosis, Lou Gehrig’s disease, is a crippling, progressive neurodegenerative disease for which there is no cure. Now it seems that a diabetes drug may help some cases.Laura P.W. Ranum, Director, Center for NeuroGenetics and Kitzman Family Professor of Molecular Genetics & Microbiology, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1294242020-02-18T13:55:36Z2020-02-18T13:55:36ZAssisted dying is not the easy way out<figure><img src="https://images.theconversation.com/files/315377/original/file-20200213-11000-c1rktt.jpg?ixlib=rb-1.1.0&rect=13%2C84%2C4311%2C2874&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The stress over their ability to swallow can provoke a great deal of anxiety in patients.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/senior-womans-hands-drinking-glass-water-1142021786">eyepark/Shutterstock.com</a></span></figcaption></figure><p><a href="https://www.nytimes.com/2019/07/08/health/aid-in-dying-states.html">One in every five Americans</a> now lives in a state with legal access to a medically assisted death. In theory, assisted dying laws allow patients with a terminal prognosis to hasten the end of their life, once their suffering has overcome any desire to live. While these laws may make the process of dying less painful for some, they don’t make it easier. Of the countries that have aid-in-dying laws, the U.S. has the <a href="https://www.bbc.com/news/world-34445715">most restrictive</a>. Intended to reduce unnecessary suffering, the laws can sometimes have the opposite effect. </p>
<p>My work as a medical anthropologist explores the field of medicine from a cultural angle, focusing primarily on <a href="https://www.press.uchicago.edu/ucp/books/book/chicago/B/bo25956731.html">birth</a> and <a href="https://undark.org/2017/10/19/death-dying-america-anthropologist/">death</a>. Over the past four years, I’ve studied how access to a medically assisted death is transforming the ways Americans die. I have spent hundreds of hours accompanying patients, families and physicians on their road to an assisted death. And, I have witnessed some of these deaths firsthand. </p>
<p>This research has taught me one thing: An assisted death is not the path of least resistance. For many, it is the path of most resistance. Those who pursue it face a range of barriers, at a time when their health is rapidly declining. Some patients navigate these waters successfully and manage to secure the coveted bottle of life-ending medication. Others give in to the opposition or simply run out of time. </p>
<h2>History of the laws</h2>
<p>The country’s first right-to-die law, Oregon’s Death with Dignity Act (1994), came after a fierce, century-long struggle to give terminally ill patients access to some form of medical assistance in dying.</p>
<p>Legislators in Ohio and Iowa proposed the first two of these bills in 1906. Known as the “<a href="https://daily.jstor.org/history-euthanasia-movement/">chloroform bills</a>,” they envisioned the use of chloroform on fatally ill or injured patients to induce their death, but their terms were so flawed that they never saw the light of day. Other <a href="https://www.finalexit.org/chronology_right-to-die_events.html">legislative bills</a> – introduced in Nebraska in 1937, Florida in 1967 and Idaho in 1969 – met similar fates. </p>
<p>When a committee of lawyers, physicians and activists sat down to craft Oregon’s <a href="https://www.oregon.gov/oha/PH/PROVIDERPARTNERRESOURCES/EVALUATIONRESEARCH/DEATHWITHDIGNITYACT/Documents/statute.pdf">Death with Dignity Act</a> in 1993, similar <a href="https://www.finalexit.org/chronology_right-to-die_events.html">ballot initiatives</a> had recently failed in Washington (1991) and California (1992). To appease vocal opposition, lawmakers laced the Oregon statute with a long list of restrictions and safeguards.</p>
<p>Unlike all previous proposals, the Oregon measure no longer allowed for euthanasia. That’s the act of injecting a patient with a lethal dose of narcotics. Under the law, patients would have to ingest the lethal dose themselves – a final protection meant to ensure the absolutely voluntary nature of their death. The act also introduced a 15-day waiting period between a patient’s first and second request, intended as a period of reflection. </p>
<p>It worked. Oregonians narrowly approved the measure, but a three-year legal stay prevented it from being enacted. In 1997, Oregonians <a href="https://ballotpedia.org/Oregon_Repeal_of_%22Death_with_Dignity%22,_Measure_51_(1997)">reaffirmed their support</a> for the act, and it became law. Since then, <a href="https://www.deathwithdignity.org/take-action/">each state</a> that has added an assisted dying law to their books has either followed the strict Oregon model or, in the case of <a href="https://www.capitol.hawaii.gov/session2018/bills/HB2739_HD1_.pdf">Hawaii</a>, added more constraints. Those include requiring a mandatory mental health exam and a 20-day waiting period in between requests. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/315114/original/file-20200212-61917-cmd00h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/315114/original/file-20200212-61917-cmd00h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=396&fit=crop&dpr=1 600w, https://images.theconversation.com/files/315114/original/file-20200212-61917-cmd00h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=396&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/315114/original/file-20200212-61917-cmd00h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=396&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/315114/original/file-20200212-61917-cmd00h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=498&fit=crop&dpr=1 754w, https://images.theconversation.com/files/315114/original/file-20200212-61917-cmd00h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=498&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/315114/original/file-20200212-61917-cmd00h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=498&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">MPs in the parliament of Victoria in Australia react after Victoria passed legislation Nov. 22, 2017 to allow assisted dying.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/harriet-shing-mp-and-colleen-hartland-mp-react-as-the-bill-news-photo/877314916?adppopup=true">Getty Images/Scott Barbour</a></span>
</figcaption>
</figure>
<h2>The letter of the law</h2>
<p>Unlike other countries that permit assisted dying, such as Canada, the Netherlands and Belgium, in the U.S. intolerable suffering and an incurable medical condition alone are not enough to qualify someone for an aided death. A patient must already be within six months of the end of their life – coinciding with the admission criteria for hospice. That means protracted degenerative diseases with open-ended prognoses like amyotrophic lateral sclerosis (ALS) don’t usually qualify, at least not until a patient’s breathing becomes severely compromised. </p>
<p>Every year, <a href="https://www.civilbeat.org/2020/01/report-too-many-people-are-dying-while-waiting-for-medical-aid-in-dying/">dozens of eligible patients</a> who apply for an assisted death are so close to the end of their life that they die during the mandated waiting period. And by the time a patient becomes eligible for an assisted death, they may have missed the window when they are able to ingest the lethal medication. In contrast to their Canadian, Dutch and Belgian colleagues, American physicians cannot administer these drugs to their patients. </p>
<p>Lou Libby, a pulmonologist from Portland, Oregon, told me that the physical manifestations of many advanced neurodegenerative diseases bump up against this requirement. Again, consider ALS. Alongside their diminishing ability to breathe, patients with ALS almost always lose their ability to swallow. </p>
<p>“You have to be able to ingest the medication yourself. And here you have all these patients who can’t even swallow.” </p>
<p>As I learned during my research, the stress over their ability to swallow can provoke a great deal of anxiety in patients, particularly when it comes to correctly timing their death. Taking the medication too early means cutting short a life still worth living; waiting too long means possibly missing their chance. To have the kind of death they prefer, some patients choose to die earlier than they would have liked.</p>
<h2>Cultural roadblocks</h2>
<p>Despite popular backing for medical assistance in dying – <a href="https://news.gallup.com/poll/235145/americans-strong-support-euthanasia-persists.aspx">seven in 10 Americans</a> support it – the cultural stigma and moral ambivalence around these laws remain potent. Across the country, many <a href="https://www.theguardian.com/society/2020/jan/28/catholic-hospitals-lead-fight-against-access-drugs-assisted-dying">religiously owned</a> health systems decline to participate in their state’s assisted dying law. </p>
<p>In <a href="https://www.bendbulletin.com/lifestyle/health/rural-oregonians-still-face-death-with-dignity-barriers/article_e41a5836-8bd6-5680-b37d-07517d3b9335.html">rural parts</a> of Oregon and along the coastal corridor, where Catholic health systems often run the only hospital in town, patients routinely struggle to find two physicians who will approve their request, or a pharmacist who will fill their prescription. <a href="https://endoflifewa.org/wp-content/uploads/2012/11/Courtney-Campbell-Hastings-Center-9-10.pdf">Many hospices</a> refuse to cooperate with a patient’s desire to seek an assisted death, leading patients to feel abandoned. <a href="https://www.nap.edu/read/25131/chapter/7#103">Many assisted living and nursing facilities</a> still prohibit the practice under their roof, forcing patients to make alternative arrangements, sometimes at a nearby motel. In trying to reclaim control over the way they die, these patients often are being stripped of some of that control in the process. </p>
<p>Medical aid-in-dying will become an even bigger issue as baby boomers face the end of their lives. It is mainly older patients who want access to an assisted death. In Oregon, for example, nearly 80% of those who sought medical assistance in dying <a href="https://www.oregon.gov/oha/PH/PROVIDERPARTNERRESOURCES/EVALUATIONRESEARCH/DEATHWITHDIGNITYACT/Documents/year21.pdf">in 2018</a> were 65 or older. Boomers, as in many other aspects of their lives, likely <a href="https://business.time.com/2013/08/14/a-good-death-how-boomers-will-change-the-world-a-final-time/">will want more say over their deaths</a>.</p>
<p>Assisted dying reframes how we, as a society, understand the potential of medicine, not as a way to extend life but to mitigate the process of dying. Patients who endure intractable, painful diseases sometimes reach a moment when the prospect of staying alive feels worse than the prospect of dying. At that point, the idea of having a say over the timing and manner of their death can bring <a href="https://www.nytimes.com/interactive/2019/12/05/sports/euthanasia-athlete.html">enormous comfort</a>. But few are aware of all the hurdles they must clear to exercise this kind of control.</p>
<p>[ <em>Like what you’ve read? Want more?</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=likethis">Sign up for The Conversation’s daily newsletter</a>. ]</p><img src="https://counter.theconversation.com/content/129424/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anita Hannig does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Nine states and the District of Columbia currently have laws that permit assisted dying, but the laws are so restrictive that they are often more hurdle than help.Anita Hannig, Associate Professor of Anthropology, Brandeis UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/706272018-03-14T18:40:35Z2018-03-14T18:40:35ZStephen Hawking as accidental ambassador for assistive technologies<figure><img src="https://images.theconversation.com/files/210290/original/file-20180314-113475-1lqlm8y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A computer-generated voice was essential to Hawking's participation in the world around him.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Hawking-Flight/279f26e4d6074167b66df1a71009fb66/14/0">AP Photo/John Raoux</a></span></figcaption></figure><p>Imagine you’ve contemplated the great scientific theories of the past and arrived at new insights based on your own observations. Imagine you’ve organized these thoughts into compelling arguments. Imagine that what you have to say will likely advance humanity’s understanding of its existence. Now imagine your frustration if you were unable to use your physical voice or hands to speak or write the thoughts coalescing in your mind.</p>
<p>Such was the situation for <a href="https://www.nytimes.com/2018/03/14/obituaries/stephen-hawking-dead.html">Stephen Hawking</a>, the great explainer of the universe, who <a href="https://theconversation.com/tributes-pour-in-for-stephen-hawking-the-famous-theoretical-physicist-who-died-at-age-76-93363">died on March 14</a>. He was a brilliant physicist <a href="http://www.hawking.org.uk/publications.html">who published more than 230 scientific articles</a>, papers, books, book chapters and children’s books. He gave countless lectures and stretched humankind’s understanding of the nature of our existence. Hawking was well-regarded by his scientific peers but also explained his thoughts in ways that make sense to everyone else. This is an unparalleled contribution for anyone, but especially for someone whose communication was severely limited by <a href="http://www.alsa.org/about-als/">ALS, or amyotrophic lateral sclerosis</a>. </p>
<p>At age 21, Hawking was given the standard two to five years to live after his ALS diagnosis. He beat the predictions. Hawking lived with the physical effects of this neurodegenerative disease for more than half a century. </p>
<p>Fortunately, Hawking lived in a time when researchers were rapidly developing electronic technology to assist people with physical limitations in achieving increased independence. Here at Montana’s <a href="http://ruralinstitute.umt.edu">University Center for Excellence on Developmental Disabilities</a>, we investigate and promote services and supports that increase quality of life, independence and integration of people with disabilities. For us, Hawking was a valuable role model for more than the next generation of scientists. With his recognizable wheelchair and computer-generated voice, he demonstrated the value of technological solutions to liberating the voice of those with physical and communication disabilities.</p>
<h2>Tech fills in for functional limitations</h2>
<p>So-called assistive technologies provide a means for people to move from place to place, to eat independently, to see and hear what they can’t otherwise perceive. They include basic things like wheelchairs to help people move around, magnifiers that increase the size of text or images to make them easier to see, even nonelectronic items like large-handled kitchen utensils that are easier to hold; think about everyday things in your kitchen drawers such as can openers, spoons, spatulas and the like.</p>
<p>Assistive technologies range from the seemingly simple all the way to speech-generating devices (SGD) that provide a physical voice to those who don’t have one. <a href="http://www.bbc.com/news/technology-33991887">Stephen Hawking’s SGD system</a> combined relatively simple technology together in a unique and functional way. <a href="http://www.hawking.org.uk/the-computer.html">In his own words he described</a> how he managed a tablet computer with an infrared switch that he controlled with cheek movements:</p>
<blockquote>
<p>“[An open source program] provides a software keyboard on the screen. A cursor automatically scans across this keyboard by row or by column. I can select a character by moving my cheek to stop the cursor. My cheek movement is detected by an infrared switch that is mounted on my spectacles. This switch is my only interface with the computer. [The open source program] includes a word prediction algorithm … so I usually only have to type the first couple of characters before I can select the whole word. When I have built up a sentence, I can send it to my speech synthesizer. … I can also control the mouse in Windows. This allows me to operate my whole computer. I can check my email… surf the internet … or write lectures. My latest computer … contains a webcam which I use with Skype.”</p>
</blockquote>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/OTmPw4iy0hk?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Stephen Hawking’s voice and the machine that powers it.</span></figcaption>
</figure>
<h2>Setting an example and normalizing SGDs</h2>
<p>Among his many accomplishments, one that might not be readily apparent was Hawking’s role as a “spokesmodel” for the use of assistive technologies. In a way, he was like a brand ambassador – a person who made the connection between consumers and products. He demonstrated throughout his adult life that technology was simply a tool that enabled him, and others like him, to fully participate and contribute to the world around him. Rather than one particular keyboard or software system, the “product” that Hawking promoted was the concept that physical limitation cannot hamper the human mind.</p>
<p>Tech solutions, all of which are part of everyday 21st-century life, are used to overcome physical limitations imposed by functional disabilities. From complex solutions used by well-known people – such as the late Christopher Reeve’s use of a high-tech wheelchair – to simpler ones like screen magnifiers on our computers and speech recognition “voice commands” on our smartphones, technology makes some tasks easier. In a very public way, Hawking demonstrated that it is OK – maybe even somewhat cool – to use technology to enhance or enable communication, to move around, work, play and fully participate in family and professional activities.</p>
<p>“Stephen Hawking is the most recognizable speech-generating device user in the world,” said Julie Doerner, the former clinical coordinator of MonTECH, a program I oversee at the Rural Institute for Inclusive Communities. MonTECH, one of 56 <a href="http://ataporg.org">statewide assistive technology programs</a> in the U.S. and its territories, loans equipment for free to Montanans with disabilities to help them with the tasks of everyday life including reading, bathing, typing, eating, or simply getting from place to place. She continued, “When I explain assistive technology devices to others, I use Stephen Hawking as an example. They all know who he is.” The response is usually, “ah, that’s cool!”</p>
<p>Hawking and other high-profile users show the world that technology is not strange, nor does it diminish or magnify them as human beings. The technology they use allows others to look past disability and focus their attention on who they are, on them as people. And Hawking’s fame raised the visibility of speech-generating technologies, helping them seem more commonplace than weird for people all over the world – both those who might need SGDs and those who might encounter others using them to communicate.</p>
<p>Advances in technology that help us interact with the world around us are <a href="https://www.entrepreneur.com/article/245192">limited only by our imagination</a>. We now take for granted that we can ask our smartphone questions, that it can guide us to our next appointment, monitor our heart rate, measure our steps, help us find and communicate with others, and on and on. Smart technologies are being incorporated into our kitchen appliances, shoes, vehicles and eyeglasses. These and the world of robotics stretch our thinking about ways in which <a href="https://www.pcmag.com/commentary/353201/the-future-of-assistive-tech-is-smart">technology can enhance human independence</a>, regardless of physical, and sometimes cognitive, limitations.</p>
<p>How these advances will benefit people with disabilities remains to be seen. One thing is certain though. The use of assistive technologies in our everyday world diminishes the differences between people with different abilities. We owe much to Professor Hawking’s example. Ah, that’s cool!</p><img src="https://counter.theconversation.com/content/70627/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Martin Blair receives funding from the U.S. Administration on Community Living. He is affiliated with the Association of University Centers on Disabilities in Silver Spring, Maryland. </span></em></p>You can probably hear Hawking’s famously computer-generated voice in your head. His example showed tech as a tool that enables people with disabilities to fully participate in and contribute to the world.Martin E. Blair, Executive Director of the Rural Institute for Inclusive Communities, and Associate Professor of Teaching and Learning, University of MontanaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/836312017-10-10T22:47:07Z2017-10-10T22:47:07ZWho will be the doctors of death in a time of assisted suicide?<figure><img src="https://images.theconversation.com/files/189070/original/file-20171005-6575-iqsezw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Medical assistance in dying has been legal in Canada since July 2016, but there are no 'specialists' responsible for doctor-assisted suicide and many doctors are overwhelmed with requests. </span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Medical assistance in dying (MAID) became a reality in Canada when <a href="http://www.parl.ca/DocumentViewer/en/42-1/bill/C-14/royal-assent">legislation was passed</a> in July 2016. This is the hastening of death through a lethal dose of medication — either by self-ingestion (assisted suicide) or physician injection (euthanasia). </p>
<p><a href="http://www.cbc.ca/news/politics/medical-assistance-death-figures-1.4344267">More than 2,000 Canadians</a> have received MAID, administered by a number of physicians. Few of those doctors are palliative care specialists, who are purposely <a href="http://www.cspcp.ca/wp-content/uploads/2015/10/CSPCP-Key-Messages-FINAL.pdf">keeping their distance from MAID</a> to avoid further stigmatization as the physicians of death. They do not want to be associated with treatment failure, or viewed as only providing care to those who have either <a href="http://nationalpost.com/health/when-to-give-up-treatment-or-comfort-for-late-stage-cancer">given up</a> or been deemed hopeless. </p>
<p>This has left MAID without leadership or co-ordination, leading to unequal access and confusion among the public and health-care providers.</p>
<p>I am a palliative care physician at Queen’s University who teaches medical students, residents and other health-care providers. I am adjusting to the new reality of palliative care in the MAID era. Many patients and families ask me about it and a fair number receive it. One patient asked me to be there for his MAID death. </p>
<p>I speak to nursing and physician groups and at <a href="http://www.queensu.ca/eventscalendar/calendar/events/barry-smith-symposium-end-life-care-death-and-dying">public events</a> where I can be simultaneously applauded and criticized for not providing doctor-assisted suicide as part of my palliative care. At these events, there is always uncertainty about MAID: the ethics, legalities, practicalities (how, where, by whom). And there are questions about the comfort of health-care providers with an intervention aiming to administer death rather than stave it off.</p>
<h2>Doctors who improve quality of life</h2>
<p>To understand why palliative care does not wish to “own” MAID requires an understanding of the <a href="http://www.who.int/cancer/palliative/definition/en/">meaning of palliative care</a>. </p>
<p>Palliative care is an approach that improves the quality of life of patients and their families facing a life-threatening illness by preventing and relieving suffering through treatment of pain and other problems — physical, psychosocial and spiritual. It is often provided alongside disease-focused treatments like chemotherapy, radiation or surgery.</p>
<p>Traditionally, palliative care has mostly provided care to <a href="http://www.cancer.ca/en/about-us/for-media/media-releases/national/2016/palliative-care-report-2016/?region=on">patients with cancer</a>, but it is appropriate for anybody with advanced diseases of organs like the <a href="https://www.heartandstroke.ca/heart/conditions/heart-failure">heart</a>, <a href="https://www.lung.ca/copd">lung</a>, <a href="https://www.kidney.ca/kidney-disease">kidneys</a> and <a href="https://www.liver.ca/patients-caregivers/liver-diseases/cirrhosis/">liver</a>. And for those with nervous system disorders like <a href="https://www.als.ca/about-als/">ALS</a> or <a href="http://www.alzheimer.ca/en/About-dementia">dementia</a>. Palliative care is also <a href="http://www.sickkids.ca/patient-family-resources/paediatric-advance-care-team/index.html">provided to children</a> with the above illnesses and also those with congenital disorders.</p>
<p>Research shows that palliative care can <a href="https://doi.org/10.1191/026921698676226729">improve symptom control</a>, <a href="https://dx.doi.org/10.1001/jama.2009.1198">quality of life</a> and, in some cases, <a href="https://dx.doi.org/10.1056/NEJMOa1000678">lead to improved survival</a>. But palliative care is still often seen as the care provided “when nothing else can be done” and when <a href="https://dx.doi.org/10.1503/cmaj.151171">someone is close to death</a>. </p>
<p>This causes problems where patients don’t want to see palliative care “too early” and their doctors are reluctant to refer for <a href="https://dx.doi.org/10.1002/cncr.24206">similar reasons</a>. This shrinks the time in which doctors can help with symptoms and care plans for the future. A large cancer centre in the U.S. noted this problem and changed the name of their “palliative care” team to “supportive care.” </p>
<p>There was an immediate <a href="https://dx.doi.org/10.1634%2Ftheoncologist.2010-0161">41 per cent increase in referrals</a> and those referrals came earlier due to less stigma around the name.</p>
<h2>Reducing suffering, not stopping life</h2>
<p>Admittedly, palliative care and MAID are both trying to treat suffering, but the methods are different: palliative care does not try to speed up (or slow down) death whereas MAID expressly speeds up death. Palliative care tries to reduce suffering by treating physical, psychosocial and spiritual distress whereas MAID stops suffering by stopping life. </p>
<p>Before MAID was legalized, patients whose suffering couldn’t be fixed by other means would get palliative sedation to reduce their awareness and suffering until they died.</p>
<p>While most palliative care doctors don’t provide MAID, we’re not all opposed to its legalization. I support a person’s choice to hasten their death if they have “grievous and irremediable” suffering, which is the terminology used in the <a href="http://www.cbc.ca/news/politics/supreme-court-says-yes-to-doctor-assisted-suicide-in-specific-cases-1.2947487">Supreme Court decision</a>. There are some patients that, despite our best interventions, still suffer a bad death. Many more patients never get the “best” intervention as they <a href="https://beta.theglobeandmail.com/news/national/canadians-lack-proper-access-to-palliative-care-study-finds/article28122378/">can’t access expert palliative care</a> where they live or the system is too overburdened to provide care.</p>
<h2>Who will be the doctors of death?</h2>
<p>So who should have responsibility for MAID? There are no “specialists” that reliably provide MAID, and many doctors struggle to manage the requests of patients. The few doctors who provide it are generally doing it on top of their regular work, risking burnout. </p>
<p>A new group — the <a href="http://camapcanada.ca/">Canadian Association of MAID Assessors and Providers</a> — provides peer support and clinical guidelines. They are also trying to keep up with a legal landscape that is <a href="https://beta.theglobeandmail.com/news/national/ontario-judge-rules-woman-fits-criteria-for-medically-assisted-death/article35375467/">changing frequently</a>, especially around the <a href="http://www.cbc.ca/news/canada/british-columbia/assisted-dying-law-canada-moro-1.4294809">“reasonably forseeable” death</a> clause which was included in the legislation but has not been defined and thus is subject to varying interpretation.</p>
<p>They are also expecting legal challenges regarding “<a href="http://www.cbc.ca/news/politics/doctor-assisted-death-minors-1.3466769">mature minors</a>” and patients with advanced directives who are not able to request MAID, such as those with advanced dementia. Currently only adults who are mentally competent to consent at the time of the MAID procedure are eligible to receive it. Nobody can ask for MAID in a living will or have their loved ones request it on their behalf.</p>
<p>In the end, palliative care doctors, providers of MAID and the public all have the same goal: to alleviate suffering, to maximize quality of life and to respect autonomy for those suffering from life-limiting illnesses. </p>
<p>Almost everyone agrees that palliative care needs to be strengthened in Canada with more education, capacity and funding. Better palliative care will mean less suffering for patients. For those who request MAID due to their suffering, they should be able to access it in an equitable, respectful and expedient way. </p>
<p>End-of-life care remains an uncomfortable but critically important topic and is really the responsibility of everyone.</p><img src="https://counter.theconversation.com/content/83631/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Craig Goldie does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>More than 2,000 Canadians have chosen medical assistance in dying (MAID) since legalization in 2016. But palliative care doctors aren’t embracing assisted suicide as part of their job.Craig Goldie, Assistant Professor, Palliative Physician, Queen's University, OntarioLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/794092017-06-19T20:00:25Z2017-06-19T20:00:25ZWhat we know, don’t know and suspect about what causes motor neuron disease<figure><img src="https://images.theconversation.com/files/173960/original/file-20170615-23574-lpx29a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Some types of MND start with a loss of grip. But what causes this?</span> <span class="attribution"><span class="source">from www.shutterstock.com.au</span></span></figcaption></figure><p><em>This is a longer read.</em></p>
<hr>
<p>Since 2014, <a href="https://www.forbes.com/sites/dandiamond/2014/08/29/the-als-ice-bucket-challenge-has-raised-100m-but-its-finally-cooling-off/#4a044fbd5cfb">the ice bucket challenge</a>, which involves people pouring a bucket of icy water over their heads, has raised awareness and much-needed research funds for motor neuron disease. While <a href="http://www.alsa.org/research/research-we-fund/">research</a> for a cure is underway, first we need to know what causes it.</p>
<p>MND affects <a href="https://www.mndaust.asn.au/Documents/Information-resources/MND-Week-background-fact-sheet.aspx">two per every 100,000</a>, or approximately 420,000 people worldwide. It <a href="https://www.mndaust.asn.au/Documents/Information-resources/MND-Week-background-fact-sheet.aspx">occurs in all countries of the world</a>, and does not discriminate based on race, ethnicity or socioeconomic status.</p>
<p>MND is the <a href="https://www.alsmndalliance.org/what-is-alsmnd/">name</a> given to a group of diseases in which the motor neurons that control muscles progressively die. <a href="https://en.wikipedia.org/wiki/Motor_neuron">Motor neurons</a> are cells in the brain and spinal cord that allow us to move, speak, swallow and breathe by sending commands from the brain to the muscles that carry out these functions. </p>
<p>Motor neurons can be divided into either <a href="http://www.medicinenet.com/script/main/art.asp?articlekey=33871">upper motor neurons</a>, which live in the main brain region and project into the brainstem and spinal cord, or <a href="http://www.medicinenet.com/script/main/art.asp?articlekey=33870">lower motor neurons</a>, which reside in the brainstem or spinal cord and directly innervate muscles.</p>
<p>Normally, upper motor neurons transmit signals to lower motor neurons, directing them to make movements. The lower neurons then signal the muscles themselves, controlling normal movements. When the signal is disrupted at some point in the pathway, it affects the ability of muscles to contract and move.</p>
<p>MND is <a href="https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Motor-Neuron-Diseases-Fact-Sheet">classified</a>, in part, by whether the upper or lower neurons are the ones degenerating and dying. In amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease, the most common type of MND, both upper and lower motor neurons are affected. Other types of MND may just affect one or the other, and each condition has slightly different symptoms.</p>
<p>Disease of the <a href="https://www.ole.bris.ac.uk/bbcswebdav/institution/Faculty%20of%20Health%20Sciences/MB%20ChB%20Medicine/Year%203%20Medicine%20and%20Surgery%20-%20Hippocrates/Neurology%20-%20Presenting%20complaints/page_29.htm">upper motor neurons</a> causes stiffness of muscles (spasticity), muscle weakness and exaggerated tendon reflexes, such as knee jerks. But if the <a href="https://www.ole.bris.ac.uk/bbcswebdav/institution/Faculty%20of%20Health%20Sciences/MB%20ChB%20Medicine/Year%203%20Medicine%20and%20Surgery%20-%20Hippocrates/Neurology%20-%20Presenting%20complaints/page_29.htm">lower are primarily affected</a>, muscles no longer receive innervation, causing them to weaken and waste away (atrophy), while also developing uncontrollable twitches (fasciculations) and losing their reflex responses.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/174359/original/file-20170619-17336-12nlryl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/174359/original/file-20170619-17336-12nlryl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/174359/original/file-20170619-17336-12nlryl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=770&fit=crop&dpr=1 600w, https://images.theconversation.com/files/174359/original/file-20170619-17336-12nlryl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=770&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/174359/original/file-20170619-17336-12nlryl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=770&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/174359/original/file-20170619-17336-12nlryl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=968&fit=crop&dpr=1 754w, https://images.theconversation.com/files/174359/original/file-20170619-17336-12nlryl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=968&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/174359/original/file-20170619-17336-12nlryl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=968&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">US baseballer Lou Gehrig was diagnosed in his 30s, and his specific type of MND became known as Lou Gehrig’s disease.</span>
<span class="attribution"><span class="source">Wikimedia Commons</span></span>
</figcaption>
</figure>
<p>If both are affected, symptoms <a href="http://brainfoundation.org.au/disorders/motor-neurone-disease">usually start mildly</a> with a loss of grip, a slurred word or stumbling while walking. The disease then <a href="https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Motor-Neuron-Diseases-Fact-Sheet">spreads</a> as motor neurons continue to die, affecting all <a href="https://en.wikipedia.org/wiki/Skeletal_muscle">skeletal muscles</a>, which are under control by the central nervous system. This leads to muscle weakness and atrophy on both sides of the body. </p>
<p>Muscles become spastic, spasm and display uncontrollable twitches. In <a href="https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Motor-Neuron-Diseases-Fact-Sheet">75% of individuals</a>, muscles of the face and throat that control speech, swallowing and chewing also become weak and waste away, leading to slurred or nasal speech and difficulty eating. Over time, the disease spreads to muscles of the diaphragm and chest, leading to an inability to breathe without mechanical support, and eventually, death.</p>
<p>Symptoms of MND can vary from person to person, and the rate of progression can also differ widely between individuals. However, it does progress in all cases. For the majority of people, this period of disease progression is quite rapid, with most living <a href="https://www.alsmndalliance.org/what-is-alsmnd/">two to five years</a> after the onset of symptoms. Only <a href="http://www.alsa.org/about-als/facts-you-should-know.html">20% of patients live for five years</a>, 10% for ten years and 5% for 20 years or more. One famous <a href="https://www.scientificamerican.com/article/stephen-hawking-als/">notable exception</a> is the theoretical physicist Stephen Hawking, who was first diagnosed at age 21 and is now 75 years old, meaning he has lived with the condition for over 50 years.</p>
<p>The cause of most cases of MND is currently unknown, although multiple hypotheses have been put forward. This is currently an area of major research throughout the world.</p>
<h2>Genetic causes</h2>
<p>A small number of cases of MND (<a href="http://www.alsa.org/research/focus-areas/genetics/">5-10%)</a> are inherited from family and can be attributed to a specific <a href="https://ghr.nlm.nih.gov/primer/mutationsanddisorders/genemutation">genetic mutation</a>, or an alteration in the sequence of DNA. It’s estimated that, currently, about <a href="http://www.alsa.org/research/focus-areas/genetics/">60% of the genes</a> associated with familial MND have been identified. For most MND genes, an individual only needs to inherit one copy of the mutated gene to cause the disease.</p>
<p>The first gene mutation to be discovered in MND was one called “SOD1”, in 1993. <a href="http://www.alsa.org/research/focus-areas/genetics/sod1.html">SOD1 mutations</a> account for about 10-20% of cases of familial MND (and 1-2% of sporadic cases). While it’s unclear exactly how changes in this gene lead to MND, it’s thought that it takes on a toxic property, leading to damage in the brain cells and, eventually, death of motor neurons.</p>
<p>Another important gene implicated in familial MND is “C9orf72”, which was found in 2011 and is known to be the most common genetic cause of MND. <a href="http://www.alsa.org/research/focus-areas/genetics/">Mutations in this gene</a> account for 25-40% of familial MND (and 7% of sporadic cases). This gene has also been shown to account for 25% of cases of another neurodegenerative disease, a type of dementia called frontotemporal dementia. </p>
<p>This gene contains abnormal repetitions in the DNA code, called <a href="http://www.als.net/news/what-is-c9orf72-what-are-we-doing-about-it/">repeat expansions</a>. While healthy individuals have up to 30 of these repetitions, individuals with MND, frontotemporal dementia or both can have hundreds or even thousands of repeats. But it’s still a <a href="http://www.sciencedirect.com/science/article/pii/S0006899316301974">matter of debate</a> how this could lead to the development of the disease, with several potential mechanisms put forward, and further research needed.</p>
<p>In addition to these two major genetic discoveries, <a href="http://www.alsa.org/research/focus-areas/genetics/">several other genes</a> have been implicated (NEK1, TDP43, FUS and UBQLN2) that appear to play a smaller role in the number of cases of MND they cause. </p>
<p>It’s important to remember, though, that genetic mutations play a small role in most cases of MND. While 5-10% of cases are familial, with a clear genetic link, the other 90-95% of cases are sporadic and are likely to be due to a complex interaction of genetic risk factors and environmental variables.</p>
<h2>Age and gender</h2>
<p>Non-genetic factors that may contribute to the development of MND have been extensively studied over the years, with several potential causes emerging. One of the major risk factors for MND is advancing age. MND is rare before the age of 40, with an <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334292/">average age of onset</a> of 58-63 years for sporadic MND and 40-60 years for familial MND. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334292/">Males</a> are also more likely than females to have MND, but we don’t know why.</p>
<h2>Lifestyle causes</h2>
<p>A number of lifestyle risk factors for MND have also emerged. <a href="https://www.ncbi.nlm.nih.gov/m/pubmed/21320987/">Smoking</a> is known to increase the risk of MND, with one study indicating smokers were 42% more likely to be diagnosed with MND, while former smokers had a 44% higher risk. </p>
<p>Certain <a href="https://www.ncbi.nlm.nih.gov/pubmed/15529299">dietary factors</a>, such as higher intake of antioxidants and vitamin E, have been shown, at least in some studies, to decrease the risk of MND.</p>
<p>Interestingly, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334292/">increased physical fitness and lower body mass index (BMI)</a> have been shown to be associated with a higher risk of MND. The diagnosis of baseballer Lou Gehrig led scientists to theorise that <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334292/">strenuous physical activity and excessive use of muscles</a> could contribute to the development of MND. </p>
<p>While evidence for this has been inconsistent, an increased risk for MND has been demonstrated among professional soccer players, and MND patients have <a href="https://mndresearch.wordpress.com/2013/12/08/physical-activity-and-mnd-is-there-a-link/">higher levels of vigorous physical activity</a> compared to individuals without MND. Other factors, however, may account for this relationship, such as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2239342/">repeated head injuries</a>, another purported cause of MND.</p>
<p>A <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334292/">number of occupations</a> have also been found to be associated with increased risk of MND, including electrical workers, farmers, house painters and military personnel. Other individuals exposed to electromagnetic fields, certain chemicals, pesticides and heavy metals, such as lead, manganese, iron and selenium, during the course of their work are also at risk. </p>
<p>But it’s still unclear how <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334292/">exposure to these toxins</a> may lead to the development of MND, and not all studies in this area have been consistent in demonstrating increased risk. Another issue with these toxin exposure studies is that many rely on self-reports, with individuals having to recall their past exposures. This can lead to <a href="http://www.alsa.org/research/focus-areas/environmental-factors/">recall bias</a>, where people with the disease are more likely to report a past exposure, leading to an over-inflation of risk.</p>
<h2>Other illnesses</h2>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334292/">Exposure to viruses</a> has also been cited as a potential cause of MND. Polio virus, for example, can infect motor neurons, and may be linked to later weakening of these neurons. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723705/">Retroviruses</a>, such as HIV, have also been shown to be potentially linked to the development of MND. </p>
<p>In addition to viruses, other medical conditions may also be linked to an increased risk of MND. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334292/">Type I diabetes</a> has been shown to be associated with a threefold increase in risk (although, interestingly, <a href="http://archneur.jamanetwork.com/article.aspx?articleid=2299316">Type II diabetes</a> was associated with a lower risk for MND). </p>
<p>Consistent with <a href="http://journal.frontiersin.org/article/10.3389/fphar.2014.00157/full">other neurodegenerative diseases</a>, such as Alzheimer’s and Parkinson’s disease, <a href="https://www.sciencedaily.com/releases/2012/06/120605121704.htm">increased inflammation</a> has also recently gained attention as a potential cause of MND. One study showed that, in MND, inflammatory cells called macrophages can ingest motor neurons.</p>
<h2>What makes treatment so complicated?</h2>
<p>Despite decades of research, there is only one treatment currently approved for MND, a drug called <a href="http://alsworldwide.org/research-and-trials/article/rilutek-riluzole">riluzole (Rilutek)</a>, first approved by the US Food and Drug Administration in 1995. This aims to reduce the release of the neurotransmitter <a href="http://web.alsa.org/site/PageServer?pagename=ALSA_Glutamate">glutamate</a> from motor neurons, which was once thought to drive the death of these neurons. But the drug doesn’t reverse nerve damage or muscle weakness caused by the disease, and only prolongs life for about three months. </p>
<p>Aside from riluzole, most current treatments such as muscle relaxants or physical therapy attempt to maintain patient quality of life.</p>
<p>In May 2017, the US approved the first new treatment for MND in 22 years, a drug called <a href="http://www.alsa.org/news/media/press-releases/approval-of-new-als-drug-050417.html">Radicava</a> (edaravone), which is expected to be on the US market by August 2017. This drug, originally developed for the treatment of stroke in Japan, was approved in 2015 for the treatment of MND in Japan and South Korea. </p>
<p>The drug aims to prevent <a href="http://www.drugdevelopment-technology.com/projects/radicava-edaravone-for-the-treatment-of-amyotrophic-lateral-sclerosis-als">damage of neurons</a>, and the company that developed it reports it can slow the physical decline of MND patients by <a href="http://www.alsa.org/news/media/press-releases/approval-of-new-als-drug-050417.html">33%</a>. </p>
<p>The drug, which is not a cure and only slows disease progression, is stunningly expensive, <a href="http://www.alsa.org/research/radicava/radicava-frequently-asked-questions.html">costing nearly US$150,000</a> a year. And patients in the last stage of the clinical trial that led to approval in the US were only followed up to <a href="http://www.alsa.org/research/radicava/radicava-frequently-asked-questions.html">six months</a>, so the long-term benefits of the drug are unknown. The drug is not yet approved for use in Australia.</p>
<p>The causes of MND are many and complex. This is further complicated by the fact we don’t know what ultimately causes the death of motor neurons when someone has MND. If we could find this out, then we may well be on the way to developing more effective, and perhaps even curative, therapies for the disease.</p><img src="https://counter.theconversation.com/content/79409/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lyndsey Collins-Praino receives funding from the Neurosurgical Research Foundation and the University of Adelaide Commercial Accelerator Scheme.</span></em></p><p class="fine-print"><em><span>Viythia Katharesan does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>While research for a cure for MND is underway, first we need to know what causes it.Lyndsey Collins-Praino, Senior Lecturer in School of Medicine, University of AdelaideViythia Katharesan, Lecturer in the School of Medicine, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/721542017-01-31T19:01:09Z2017-01-31T19:01:09ZMind-reading technology lets locked-in sufferers communicate – and they report feeling happy<figure><img src="https://images.theconversation.com/files/154982/original/image-20170131-13264-1m4ih87.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Opening the gate to communication.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The technology to control a computer using only your thoughts has <a href="http://www.annualreviews.org/doi/pdf/10.1146/annurev.bb.02.060173.001105">existed for decades</a>. Yet we’ve made limited progress in using it for its original purpose: helping people with severe disabilities to communicate. Until now, that is. A new study has shown that an alternative brain-computer interface technology can help people with “locked-in syndrome” speak to the outside world. It has even allowed sufferers to report that they are happy, despite the condition.</p>
<p>The final stages of the degenerative condition known as <a href="http://www.alsa.org/als-care/augmentative-communication/communication-guide.html">amyotrophic lateral sclerosis</a> (ALS) or motor neuron disease, leaves sufferers in a complete locked-in state. In the end they cannot move any part of their bodies, not even their eyes, although their brains remain unaffected. But scientists have struggled to use brain-computer interface technology that measures electrical activity in the brain to help them communicate.</p>
<p>One reason for this is that it is still unclear how much these conventional brain-computer interface systems rely on electrical signals that are generated by the movement of eye muscles. One ALS sufferer who had been using a brain-computer interface when she could still move her eyes <a href="http://dx.doi.org/10.1016/j.clinph.2010.08.019">lost her ability to communicate</a> through the technology after becoming completely locked-in. This suggested that most of the electrical activity recorded by the computer was related to involuntary eye movements that occurred when she thought about something rather than the thoughts themselves.</p>
<h2>Oxygen monitoring</h2>
<p>To overcome this problem, an international group of researchers used a different way of detecting neural activity that measures changes in the amount of oxygen in the brain rather than electrical signals. The research, published in <a href="http://publiclibraryofscience.pr-optout.com/Tracking.aspx?Data=HHL%3d%3e146%3b%26JDG%3c%3a2%3a4%3b3%3d%26SDG%3c90%3a.&RE=MC&RI=5005115&Preview=False&DistributionActionID=18212&Action=Follow+Link">PLOS Biology</a>, involved a technique known as <a href="http://www.spectroscopyeurope.com/articles/55-articles/3258-measuring-brain-activity-using-functional-near-infrared-spectroscopy-a-short-review">functional near-infrared spectroscopy</a>, which uses light to measure changes in blood oxygen levels. Because the areas of the brain that are most active at any given time consume more oxygen, this means you can detect patterns of brain activity from oxygen fluctuations.</p>
<p>This technique is not as sensitive to muscular movements as the electroencephalography (EEG) systems used to measure electrical activity. This means the new method could be used to help ALS sufferers communicate both before and after they lose their entire ability to move because it is more likely to only record brain activity related to thoughts.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/154969/original/image-20170131-13220-agqn6e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/154969/original/image-20170131-13220-agqn6e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/154969/original/image-20170131-13220-agqn6e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/154969/original/image-20170131-13220-agqn6e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/154969/original/image-20170131-13220-agqn6e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1130&fit=crop&dpr=1 754w, https://images.theconversation.com/files/154969/original/image-20170131-13220-agqn6e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1130&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/154969/original/image-20170131-13220-agqn6e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1130&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">I know what you’re thinking.</span>
<span class="attribution"><span class="source">Wyss Center</span></span>
</figcaption>
</figure>
<p>The study involved four ALS sufferers, three of which had not been able to reliably communicate with their carers since 2014 (the last one since early 2015). By using the new brain-computer interface technology, they were able to reliably communicate with their carers and families over a period of several months. This is the first time this has been possible for locked-in patients.</p>
<p>The volunteers were asked personal and general knowledge questions with known “yes” or “no” answers. The brain-computer interface captured their responses correctly 70% of the time, which the researchers argued was enough to show they didn’t just record the right answer by chance. Similar experiments using EEG didn’t beat this chance-level threshold.</p>
<p>The patients were also able to communicate their feelings about their condition, and all four of them repeatedly answered “yes” when they were asked if they were happy over the course of several weeks. One patient was even asked whether he would agree for his daughter to marry her boyfriend. Unfortunately for the couple, he said no. The volunteers have continued using the system at home after the end of the study.</p>
<h2>Groundbreaking research</h2>
<p>As I know from my own research, working with completely locked-in patients requires a lot of hard work. In particular, you can’t know for sure if the user has understood how we want them to give an answer that we can try to detect. If a system that has previously been used to record the brain activity of able-bodied users doesn’t work with locked-in patients, it is common to assume that the person, and not the machine, is at fault, which may not be the case. What’s more, there is added pressure on researchers – from the patient’s family and from themselves – to fulfil the dream of finding a way to communicate with the volunteers.</p>
<p>These challenges highlight what a significant achievement the new study is. It is a groundbreaking piece of research that could provide a new path for developing better brain-computer interface technology. Even though the system so far only allows locked-in patients to give yes or no answers, it already represents a big improvement in quality of life.</p>
<p>The first ever brain-computer interface system was designed to enable disabled (although not locked-in) users to spell words and so communicate any message they wanted, admittedly through a <a href="http://www.pnas.org/content/112/44/E6058.short">slow and lengthy process</a>. So it is safe to assume that the new technology is just the first step towards more sophisticated systems that would allow free two-way communication not based on simple questions.</p>
<p>Perhaps more importantly, the technology has already restored the communication capabilities of four people who had been mute for years. Imagine how these patients and their families must have felt when they were finally able to “speak” again. Despite the challenges in brain-computer interface research, results like this are what make us keep going.</p><img src="https://counter.theconversation.com/content/72154/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ana Matran-Fernandez does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A new kind of brain-computer interface has helped ALS sufferers who cannot move to communicate.Ana Matran-Fernandez, Post-doctoral Researcher, University of EssexLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/309002014-08-27T01:47:05Z2014-08-27T01:47:05ZCritics pour cold water on the Ice Bucket Challenge: are they right?<p>The <a href="http://www.mndaust.asn.au/Get-involved/Ice-Bucket-Challenge.aspx">Ice Bucket Challenge</a> has been called “one of the most viral philanthropic social media campaigns in history”. The campaign has raised the profile of the <a href="http://brainfoundation.org.au/medical-info/8-amyotrophic-lateral-diseases">Amyotrophic Lateral Sclerosis</a> (ALS). But some have questioned whether campaigns like this one should really be looked at in such a positive light.</p>
<p>There is no disputing the public impact of the campaign. In the past few weeks the Ice Bucket Challenge — a fundraising drive to support ALS research and patient services — has spurred large-scale philanthropic activity. The New York Times reports that <a href="http://www.nytimes.com/2014/08/22/business/media/ice-bucket-challenge-donations-for-als-top-41-million.html?_r=0">contributions totalled US$41.8 million</a> between July 29 and August 21, attracting more than 739,000 new donors.</p>
<p>This seems a welcome development. After all, ALS is a debilitating disease that affects a significant number of people throughout the world. Alleviating the suffering of people who have the disease is surely a worthwhile goal.</p>
<h2>Focusing on the charitable self</h2>
<p>One worry concerns the motives of people giving. Do contributors care deeply about ALS, or do they just want to attract the esteem of others? </p>
<p>This worry seems misplaced. Even if people have mixed motives for promoting a good cause, it is still good that they promote it. And if people are more likely to give when they can gain some public recognition by doing so, fundraisers should take advantage of this. </p>
<p>Another worry is that such campaigns encourage people to respond immediately and unthinkingly when giving. Giving without thinking not only risks failing to do good, it may also lead us to do harm; some have argued that this was the case with the (similarly viral) <a href="https://theconversation.com/viral-video-gone-bad-kony-2012-and-the-perils-of-social-media-5925">KONY2012 campaign</a>.</p>
<p>We share these concerns about philanthropic campaigns. In the case of the Ice Bucket Challenge, however, it’s quite hard to see how donations to this cause could do more harm than good, or would do no good at all. </p>
<h2>The ‘bang for buck’ critique</h2>
<p>A stronger criticism of the Ice Bucket Challenge is that there are alternative ways of spending charitable donations that would bring about greater good. ALS affects roughly two in every 100,000 people, and some have suggested that charitable donations could do more good if spent on things like <a href="https://theconversation.com/poorest-children-twice-as-likely-to-catch-malaria-15350">bed nets to protect people from malaria</a>.</p>
<p>Fighting malaria is a worthy goal, but do people really have a duty to bring about the biggest bang for their charitable buck? Do they act wrongly by responding to the needs of ALS sufferers instead? </p>
<p>Some moral doctrines, such as so-called <a href="http://plato.stanford.edu/entries/consequentialism/">act consequentialism</a>, require that we aim to do what will bring about the best consequences. So donating to ALS when you can instead help buy malaria nets is wrong, according to such doctrines, when protecting people from malaria would do more good. </p>
<p>There are well-known objections to this kind of doctrine. One is that trying to bring about the best consequences can be debilitating and counterproductive, given the enormous difficulties involved in calculating the consequences of our actions.</p>
<p>More importantly, it seems unfair (not to mention churlish) to criticise someone who makes a meaningful contribution to an important cause that they care about just because some other cause is deemed more important. Criticising people for not getting the biggest bang for their charitable buck risks turning them off the idea of philanthropic giving altogether.</p>
<h2>Doing some good in a world of need</h2>
<p>If there were only a few morally important goals and we could easily say whose job it was to pursue each of them, we might then criticise people for doing something else instead. But our world is one in which there are morally important goals everywhere we look, and it is not clear whose job it is to pursue which goal. It’s not wrong to commit to helping one group of people in severe need, just because there are many other people in severe need.</p>
<p>We should distinguish doing what brings about the best consequences from doing what can be expected to bring about good consequences. It would take a great deal of research to find out which single charity does the most good with the least resources, but taking a look at websites <a href="http://www.givewell.org/">Givewell.org</a> for evidence about which are generally more efficient is surely a good start. Choosing a cause with almost no impact when you can instead choose a cause with a great deal of impact seems wrong. </p>
<p>So getting some bang for your buck matters, even if getting the biggest bang for your buck isn’t all that matters. Contributing to causes that you care about and feel invested in matters too.</p><img src="https://counter.theconversation.com/content/30900/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christian Barry receives funding from the Australian Research Council and the Research Council of Norway</span></em></p><p class="fine-print"><em><span>Holly Lawford-Smith receives funding from the European Commission (Marie Curie FP7) .</span></em></p>The Ice Bucket Challenge has been called “one of the most viral philanthropic social media campaigns in history”. The campaign has raised the profile of the Amyotrophic Lateral Sclerosis (ALS). But some…Christian Barry, Director of the Centre for Moral, Social, and Political Theory , Australian National UniversityHolly Lawford-Smith, Philosopher, University of SheffieldLicensed as Creative Commons – attribution, no derivatives.