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Why Alzheimer’s research is failing to hit treatment targets

Why Alzheimer’s research is failing to hit treatment targets

Since Alois Alzheimer first described a “peculiar severe disease” in 1901, research into dementia has grown at an astonishing rate. As the prevalence of Alzheimer’s disease increases, the need for a treatment becomes more pressing and scientists trying to understand the disease are more accountable than ever. While there has been significant investment and encouraging progress, therapies are still limited. And as the pressure on those affected by and working in the field of Alzheimer’s intensifies, therapeutic goals seem increasingly elusive and sometimes contradictory.

In comparison to other diseases such as cancer, cardiovascular disease and HIV, finding treatments for Alzheimer’s disease (AD) has been something of a biomedical flop. But measuring the achievements you get from research against the money and time expended is not straightforward. There is no way to predict a discovery timeline, and one clinical story may be longer than another. Nonetheless, costs need justification, and while pharmaceutical companies can pick and choose where they spend their money (and many are choosing not to invest in AD), academics need to defend their data to attract funding and continue the work they are convinced will reap benefits.

So can the failure of AD research to produce drugs be attributed to finance? Possibly. Dementia research is indisputably underfunded, relatively speaking. However, the important difference could be more molecular than monetary.

Cause and effect

Unlike cancer and HIV in particular, which are very well characterised experimentally, the cause (or causes) of AD, what the changes are that take place in the brain that lead to dysfunction, are still debated among scientists. Research has pointed the finger at potential culprits, but differentiating between those responsible and which get caught up as downstream effects is challenging. So while further and increased investment in research will inevitably reveal more on the causes, the lack of money may not be enough to explain why it remains so tough to decipher.

Being a disorder of the brain makes AD hard to study, diagnose and treat. Taking a biopsy from such an inaccessible organ is far more invasive than from a peripheral tumour. The pharmaceutical history of Alzheimer’s disease is an interesting one. Although several symptomatic treatments are available, no disease-modifying drug has been approved which can slow, halt or reverse cognitive decline.

Research is continuously uncovering new targets and some of these are showing real promise in phase III trials. Genetic information along with a wealth of experimental data identified the amyloid beta protein as a possible molecular basis for AD. It is now the target of several therapeutic interventions. Nevertheless, none of these have fully passed through clinical trials.

All about targets and timing. john skewes/Flickr, CC BY-ND

There could be many reasons for the lack of success: is the target being reached? Is the target correct? Is there another target that needs to be reached at the same time? Is the target being reached, but too late?. But regardless of the science, these clinical studies generate disagreement and create commotion in an already tumultuous field. Assimilating the massive amounts of data published on the causes of Alzheimer’s is impossible. Even the most open-minded researcher will have a theory they are obliged (and funded) to doggedly pursue, making it hard to challenge their personal status quo and which leaves the community as a whole with a set of conflicting ideas and irreconcilable data.

Exposure

These conflicts do not remain in an academic silo. The rising incidence of Alzheimer’s has come alongside a changing media which disseminates and discusses the results of research like never before. Increased media exposure is certainly positive in some respects; it gives the public information, helps to make scientists accountable, and stimulates important debate, but it can also be provocative.

Translating laboratory findings to the public domain can be tricky. Alexander Raths/Shutterstock

Much of the research that the public hears about is is contradictory and sometimes, although likely unintentionally, inflammatory. Headlines describing Alzheimer’s as a transmissible disease are simultaneously fascinating and alarming. And of course, the cautious inferences and caveats often contained within research can be difficult to get across in the media.

Accessible knowledge helps shape opinions, but may not always provide a complete story, and can place a strain on the relationship between those inside and outside of the laboratory.

Of course, regardless of the immense challenge, dedicated and intense research into Alzheimer’s disease must continue. High-risk, high-reward science is intellectually alluring and creates a competitive environment, a double-edged sword that can both promote and prevent scientific endeavour. There are certainly stepping stones forming in the swamp of information on Alzheimer’s that will undoubtedly grow and coalesce; progress is inevitable despite the baffling complexity of the disease. Researchers will continue to agree, collaborate, argue and oppose but ultimately the goal is the same for all, to untangle the mysteries of this devastating disease.

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