Trials to treatments: vaccines for Parkinson’s
When we think about vaccinations, we generally associate them with infectious conditions like meningitis and tuberculosis rather than Parkinson’s. But now there is promise for vaccines in clinical trials for Parkinson’s.
Using vaccination, over the last 100 years we’ve been able to almost entirely wipe out conditions such as smallpox and polio. Vaccinations are a simple way of preparing our bodies to tackle unwanted infections.
When we have a vaccination, we are injected with tiny fragments of the virus that causes the illness. These fragments are not enough to make us ill. But they do allow our bodies to generate an immune response, a defence against the foreign invader.
Specialised proteins called antibodies make up part of this defence. These help identify and mark foreign invaders for destruction, as they trigger other cells to come and destroy them.
Antibodies are very clever proteins. As well as being part of our bodies defence system they act as this system’s memory. So if our body is infected with the same foreign invader, we already have the weapons to defend ourselves.
We are probably fighting infections all the time but because of this memory to rapidly fight the invader, we do not even notice the infection. This is how vaccination works, if we have a flu jab for instance then this allows our body to make and store the weapons to fight this particular strain of flu. When we come across the same strain of flu after vaccination we should be able to fight it off with these stored weapons without becoming ill.
How could this work for Parkinson’s?
Parkinson’s is not an infectious illness. So how could a vaccine help?
If we look towards cancer, not an infectious disease, there has been success using the body’s immune response to target cancer cells. For instance using cells from the immune system to stop the growth of cancer cells or mark them for destruction. These treatments are referred to as immunotherapies and you may have seen this word in the headlines. A similar approach of using the body’s own immune response to slow down Parkinson’s is currently being studied.
Brain cells are lost in Parkinson’s and research has shown that in these brain cells there is a build-up of a sticky protein called alpha-synuclein. These sticky proteins form clumps called Lewy bodies which may play a crucial part in the death of these vital brain cells. This makes alpha-synuclein a good target to slow down Parkinson’s.
So, scientists have designed weapons, antibodies, that recognise sticky alpha-synuclein as a foreign invader as a way to protect these vital brain cells. These antibodies have been produced in the lab and are then injected into the body to help the immune system to identify, and remove the alpha-synuclein protein and stop brain cell death in Parkinson’s. This is an example of passive vaccination, as you are providing the antibodies from outside of the body. This will not allow the memory function of the defence system but should still successfully target alpha-synuclein. Most clinical trials of vaccines for Parkinson’s are of this type.
There is a second method which is an active vaccination approach which works like a flu vaccination. The active approach could help the immune system develop memory and potentially target alpha-synuclein over a longer period of time.
Will it work?
Dr Patrick Lewis, University of Reading explains
“Most of the early work on vaccines for brain disorders comes from research into Alzheimer’s. Scientists investigated ways to clear lumps of protein (called amyloid beta), which accumulates in clumps called plaques, in 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 led to a decrease in the accumulation of amyloid in their brains.
“This gave researchers hope that using a similar approach in Parkinson’s might be beneficial. In 2004, they treated mice engineered to develop these clumps of alpha synuclein with a vaccine designed to generate an immune response. This seemed to clear some of the protein.
“ The early stage trials have indicated that this approach is safe in humans, and so we will have a better idea as to whether this makes a difference in terms of slowing down Parkinson’s in the next few years.”
Overcoming hurdles of autoimmunity
It is not just in Parkinson's that vaccines are being developed. In Alzheimer’s research they are developing vaccines against the protein amyloid beta. Back in 2002 one of these vaccines was abandoned when multiple people fell ill due to an auto-immune response where the body attacks itself. This halted research into a vaccine for Alzheimer’s but now a promising vaccine, UB-311, is currently coming to the end of phase II clinical trials. A lot has been learnt from Alzheimer's trials that will benefit research into a vaccine for Parkinson's.
Where are we now?
There are multiple vaccines that have been developed targeting alpha-synuclein at various stages of clinical trials.
So let’s see what’s happening with potential vaccinations for Parkinson’s…
This is the first of three examples of what we call passive vaccination where an antibody has been designed outside of the body to be injected in, to target alpha-synuclein. Biogen and Neurimmune, two biotech companies, are developing an antibody designed specifically to stick to these clumps of alpha-synuclein and prevent them from spreading and having toxic effects on brain cells.
A completed phase I trial in 48 people without Parkinson’s and 18 people in the early stages of Parkinson’s showed that BIIB054 is safe at a range of doses.
Recruitment has just finished for a phase II trial (SPARK) in 300 people with early, untreated Parkinson’s. This research is happening in different countries including the UK, US, Italy and Spain. Participants will be randomised to receive monthly doses of either BIIB054 or a placebo, directly into the blood, for two years.
The biotech companies Prothena and Roche, are developing Prasinezumab PRX002 an antibody that binds specifically to clumps of alpha-synuclein.
A completed phase I randomised placebo trial was carried out in 80 people. Results were published in June 2018 saying that the treatment was safe and and there was reduced alpha-synuclein in the blood. Again this is good because this will lead to less protein being able to form sticky clumps.
So a larger and longer phase II clinical trial named PASADENA is currently being recruited to in the US, Austria, France, Germany and Spain.
AstraZeneca and Takeda have developed MEDI1341, this is an antibody that is again targeting clumps of alpha-synuclein. They are currently recruiting 48 healthy people to a phase I trial in the US.
We finish with an example of an active vaccination, where fragments resembling alpha-synuclein, are injected into the body to raise an immune response. As well as targeting sticky alpha-synuclein, it also triggers the immune system's memory.
Recently Affiris, a biotech company based in Austria working with the Michael J Fox Foundation, completed a clinical trial of AFFITOPE PD01A in 32 people. The active vaccination was given in two different doses over four months. Booster injections were administered 2.2 years and 3 years after the first injection
Results were published in March 2018 declaring the vaccine to be safe. The vaccination caused an immune response and antibodies were produced specifically against alpha-synuclein leading to a decline in alpha synuclein levels in the blood. This will ultimately lead to less protein being able to clump together.
Now plans are in place for a phase II clinical trial. They will conduct a much larger and longer trial to be sure that the vaccine really is safe and beneficial for people living with Parkinson’s.
The future of vaccinations for Parkinson’s
Targeting alpha-synuclein offers a promising way to stop the toxic effects of this protein in Parkinson’s. But before we see these vaccines available, more trials will need to be done to see the long-term safety and impact on symptoms and progression.
This isn’t the only way researchers are tackling alpha-synuclein. Similar trials of treatments that target alpha-synuclein are being carried out through more conventional drug development channels.
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