Affiris, a biotech company based in Austria, and the Michael J Fox Foundation, have announced the latest results of a vaccine they have been developing to treat Parkinson’s disease. Following the first stage of clinical trials, the results show promise of a vaccine that can combat the neurodegenerative disorder.
The idea of using some form of vaccine to help treat degeneration in the brain has been around for over 15 years. In a way this is a little surprising, as most people would associate vaccines with attempts to prevent infectious diseases such as tuberculosis or polio, rather than chronic diseases of the brain that don’t have an obvious link to bacteria or viruses.
The way vaccines work is by helping the immune system, giving the cells in the body that are responsible for getting rid of foreign bodies such as bacteria advanced warning of what those invaders might look like.
Developing vaccines
Most of the early work on vaccines for brain disorders comes from research into Alzheimer’s disease. Scientists investigated ways to clear lumps of protein (called amyloid beta), which accumulates in clumps called plaques, from the brains of people with dementia. They were able to show that vaccinating mice, engineered to develop some of the plaques seen in Alzheimer’s, with little fragments of this amyloid protein led to a decrease in the accumulation of amyloid in their brains.
Following this, researchers discovered that if you artificially produced antibodies (one of the most important bits of the immune system, which tag foreign objects for removal) to recognise amyloid and injected them into mice with amyloid plaques, then again you could clear away some of these clumps of sticky protein.
From Alzheimer’s to Parkinson’s
Although there are important differences between Parkinson’s disease, which mainly affects the control of movement, and Alzheimer’s disease, which affects memory and cognition, the accumulation of sticky proteins is a common feature of both diseases. In Parkinson’s, the aggregated protein is called alpha synuclein, and the lumps it forms inside cells are called Lewy bodies.
This gave researchers hope that using a similar approach in Parkinson’s might be beneficial. So, in 2004, when they treated mice engineered to develop these clumps of alpha synuclein with a vaccine designed to generate an immune response it seemed to clear some of the protein.
In the meantime, drug companies had started to check whether using vaccines in patients with Alzheimer’s could slow down the disease. The results were disappointing, mainly due to a severe side effect called an autoimmune reaction – essentially the body attacking itself. This halted research into vaccines for brain disease for a number of years, and still makes companies very cautious about going down this road.
The new approach
This is where the new approach used by Affiris comes in. An approach has been developed to reduce the possibility that the body will start attacking itself (using a technology called Affitopes) and showed in mouse models that they could generate the antibody response they were looking for with a small fragment of alpha synuclein.
What the team has now reported are the results of the first part of a clinical trial for this approach: showing that the vaccine doesn’t harm people (called a phase one trial), partly funded by the Michael J Fox Foundation. And in this it seems to have been successful. The vaccine was given to 24 people in the early stages of Parkinson’s, with eight people given a control, placebo injection at the same time. None of those given the vaccine developed the severe adverse reaction seen in some of the Alzheimer trials.
The patients were also examined to see whether they developed antibodies against alpha synuclein, and promisingly some of them did (although not all). Finally, they were assessed for changes in their Parkinson’s and – although this was a small, preliminary trial and the results need to be treated with caution – there was some evidence that the vaccine slowed down the progress of the disease.
Those with Parkinson’s now
As with any new drug, there is a lot of work to be done before we know whether the treatment really makes a difference. First of all Affiris is planning a follow up for this phase one trial, where they give the same people from the original trial a follow up or “booster” injection to see if this is safe and whether it improves some of the measurements they made in the first trial.
They then need to carry out careful evaluation in a much larger group of patients – hundreds, rather than 32 – and show that even if the patients don’t know whether they are being given the vaccine or a placebo they show some kind of benefit (a so-called blinded trial).
This is a long, slow process – a point highlighted by the Affiris medical officer, Dr Achim Schneeberger, who said that even if all of the follow-up trials went perfectly and they see real benefits for patients, it would be six to eight years before the vaccine would available generally. But this announcement marks the first step on this journey, and as such provides a glimmer of hope to patients with Parkinson’s.