Parkinson’s research highlights in 2018
It’s our last blog of the year, so we reflect on a busy and productive 2018 for Parkinson’s research and share some of our highlights.
1. New clues to the origins of Parkinson’s
In Parkinson’s, sticky bundles of a protein called ‘alpha-synuclein’ are found inside affected brain cells and are believed to play a role in the damage that causes these precious cells to die.
This year, new clues to why and how this toxic protein accumulates have been uncovered, opening up new ideas and avenues for developing treatments.
In November, scientists pinpointed another protein called USP-13 which may be a crucial player in the alpha-synuclein story.
In healthy cells, toxic or damaged proteins are labelled with a tag that marks them for destruction. This process means cells can get rid of unwanted proteins, preventing them from building up and causing problems.
USP-13 removes these destruction tags and appears to be overactive in brain cells affected in Parkinson’s — potentially playing a role in unwanted proteins, like alpha-synculein, hanging around too long. Encouragingly, the team found that reducing activity of USP-13 protected brain cells from damage in mice.
In October, researchers in the US discovered that removing the appendix in early life reduces the risk of developing Parkinson’s by 19 to 25 percent.
The team also studied appendix samples from healthy people and identified the presence of clumps of alpha-synuclein protein. These findings add further weight to the idea that, in at least some Parkinson’s cases, alpha-synuclein bundles may appear first in the gut and travel via nerve pathways into the brain.
Treatments that target alpha-synuclein are already being tested in clinical trials around the world, and there are more promising approaches on the horizon.
2. Study launches to predict Parkinson’s
We now believe that the changes in the body that lead to Parkinson’s may start many years or even decades before an individual develops the classic symptoms — such as tremor, stiffness and slowness — that lead to diagnosis.
This ‘pre-symptomatic’ period (sometimes called the ‘prodromal phase’) offers the best chance to intervene with new therapies that could fix the problems and potentially prevent people developing Parkinson’s altogether.
But how do we identify people in these early stages? We are starting to spot some of the early warning signs that someone is developing the condition — things like sleep problems, mood changes and constipation — but we have a lot more to learn before we can confidently predict who will develop Parkinson’s.
This year saw the launch of Predict PD, a large study focusing on the early signs of Parkinson’s. The UK-wide study, funded by Parkinson’s UK, is seeking 10,000 people aged 60–80 without Parkinson’s.
The aim is to find clues to the very earliest stages of the condition to help understand who may be more likely to get Parkinson’s. This will hopefully assist the development of tools that identify individuals at high risk and lead to earlier diagnosis.
This should also accelerate the development and testing of new treatments that aim to slow or stop the condition as many of these emerging therapies are likely to be most effective when used in the early stages of the condition.
3. Accelerating drug development with artificial intelligence
The traditional approach to developing new and better treatments for any medical condition is costly, and it often takes decades to get a new drug to the people who need them.
This year Parkinson’s UK and The Cure Parkinson’s Trust successfully joined forces to win a new partnership with a leading British artificial intelligence company, BenevolentAI, to use AI to unlock the masses of existing research data to deliver new therapies, faster.
The aim is to identify at least three currently available medicines that can be repurposed to address Parkinson’s, and two brand-new ways to treat the condition with new drugs.
This may sound ambitious but BenevolentAI have already achieved similar successes in other conditions including motor neurone disease.
Any promising new opportunities uncovered through this pioneering approach will be rapidly taken forward for further development and testing through our Parkinson’s Virtual Biotech.
4. Steps forward for stem cell therapies
One of the most promising avenues for developing new treatments is the use of stem cells. They are the original cells from which we are made and are responsible for repairing our tissues and organs when they get damaged. It is because of their regenerative capacity that researchers have been trying to find ways to use them to treat Parkinson’s and many other conditions.
The hope is that we may be able to use stem cells to grow new healthy brain cells that can be used to replace those lost in Parkinson’s.
Huge progress has been made in the field in the last decade in developing and refining the way stem cells can be manipulated and grown in the lab and in August this year researchers in Japan announced the first cell transplant trial for Parkinson’s to use dopamine-producing brain cells made from stem cells.
And this is far from the only clinical trial underway exploring the potential of cell-based therapies for Parkinson’s. Alongside this, there are many other ongoing studies including the EU-funded study TRANSEURO that aims to test the safety and effectiveness of transplanting brain cells collected from foetal tissue into the brains of 40 people with Parkinson’s. The phase 1 trial, which involves the collaboration of researchers from several European countries, including the UK, is well underway and is due to finish in 2019.
5. Progress towards better clinical trials for Parkinson’s
Researchers and drug companies have a new tool in the search for better treatments for Parkinson’s — a brain scan that can be used to select the right people for clinical trials.
This represents the first major success of Critical Path for Parkinson’s Consortium — a global consortium to improve clinical trials led by The Critical Path Institute in partnership with Parkinson’s UK.
As mentioned previously, because Parkinson’s is a progressive condition, caused by the gradual loss of cells in the brain, the best chance to intervene with treatments that can slow, stop or reverse the damage is during the earliest stages of the condition.
However, during these early stages, symptoms tend to be mild which makes selecting the right people to participate in trials very difficult.
Up to 15% of individuals taking part in clinical trials for new Parkinson’s treatments may have a benign form of the condition that means their symptoms do not significantly worsen over time.
These individuals are extremely unlikely to benefit from the new therapies being tested, and their inclusion can affect both the trial results and ultimately the future of the potential treatment.
“These brain scans in themselves are not new, but until now there has not been a clear consensus that they can and should be used to select participants for clinical trials,” said Diane Stephenson, Executive Director of CPP, who led the work.
“This success is just the first in a suite of new tools that we hope to deliver for Parkinson’s.”
Despite decades of research and major breakthroughs in our understanding of Parkinson’s, a cure always seems to be 5…medium.com
What are your research highlights from 2018?
So those are our highlights but what do you think? We asked some of our Research Support Network members to pick out theirs, and we’d love to hear yours in the comment section below.
“In this last year, I have realised computers make a great difference in all areas of Parkinson’s research. Such as speeding up the search for drugs for repurposing, in stem cell therapy and immunotherapy.
“After attending a recent conference on artificial intelligence, I’ve learnt that machine learning algorithms will allow these computer systems to predict the best outcome for Parkinson’s treatment.”
“Whilst there remains limited prospect of new treatments becoming widely available within the next few years, 2018 may be looked back on as a pivotal year in Parkinson’s research, with both the stem cell transplantation clinical trial in Japan and the Blue Rock embryonic stem cell trial in the US beginning human clinical trials, offering genuine hope of regenerative medicine within the near future.
“There was also significant progress in understanding the genetics, with great work being done out of the University of Dundee in relation to both LRRK2 and Parkin/ PINK1.
“We approach 2019 with renewed hope that the better management of Parkinson’s will be realised within a timeframe relative to our conditions.”
John and Sue:
“Everyone with Parkinson’s exhibits different combinations of symptoms and so clinicians are not able to tailor therapies or predict progression, quickly and reliably yet.
“The 100,000 Genomes Project has shown that it will soon be possible to identify genetic subgroups in Parkinson’s which may cause this variability. Better genomic typing should lead to smarter drug trials and personalised treatments.”
The Research Team wishes you a lovely festive season and a happy new year. See you in 2019 for more news, explanations, and perspectives.