Parkinson’s update: Why momentum is building in the hunt for new treatments and earlier diagnosis

Parkinson’s disease is the fastest growing neurological disorder worldwide, with a current dearth of disease-modifying therapies due to late diagnosis and the lack of a reliable diagnostic test. Research undertaken over the last decade, however, has contributed to a better understanding of the condition’s causes and mechanisms, helping to advance new treatments and avenues of investigation. Stephanie Price catches up with Parkinson’s UK to find out what the future holds.

From a wristwear device for low-level electrical stimulation to help with tremours, to exploring probiotics and gut microbiome changes – numerous innovative approaches to treatments along with technological advancements in Parkinson’s research are now offering new hope for patients.

Parkinson’s UK has had a crucial role in providing funding for such advancements, and the organisation has now launched the Parkinson’s Virtual Biotech, a platform which aims to accelerate drug development, investing £30m in 17 projects.

The organisation has also launched its Landmarks Project, which uses big data and donated brain tissue to speed up drug development. The project hopes to identify causal risk genes and develop new drug targets, with a budget of nearly £8m.

NR Times spoke to Parkinson’s UK research communications lead, Katherine Fletcher, to find out about the organisation’s latest research initiatives and clinical trials, and discussed the latest new treatments to reach patients.

Parkinson’s UK Landmarks Projects and Virtual Biotech

Parkinson’s UK has recently launched its groundbreaking, three-year research programme, the Landmarks project – a collaboration between Parkinson’s UK, Imperial College London, GSK, Novartis, Roche and UCB.

Backed by a founding gift of £4m from the Gatsby charitable foundation, and with a budget of £8m, the project aims to understand the condition in detail by using single nucleusRibonucleic Acid sequencing (snRNAseq) to quantify hundreds of tissue samples from the Parkinson’s UK Brain Bank, in order to create a map of gene expression in Parkinson’s across different cell types. Parkinson’s UK has confirmed that the research will also seek to better understand changes in gene expression related to the condition in order to gain insight into which genes cause risk, potential targets for new treatments, ways of measuring progression of the condition, as well as causes of Parkinson’s and Parkinson’s dementia. “The Virtual Biotech aims to make sure research doesn’t stall due to a lack of funding,” says Fletcher.

“We work in partnership with the Parkinson’s Foundation, which is a US-based charity, and The Michael J Fox Foundation is funding some of the projects that are coming through the Virtual Biotech, so it really is becoming a movement, and we work with companies all over the globe, not necessarily just UK based research.

“We have a team of people within the charity who have years and years of experience in the biotech or pharma world, and they are leading this work. They are taking their expertise from their career and hunting out opportunities and attending scientific meetings across the globe to attract ideas.”

Insights gained from the research will feed into the Parkinson’s Virtual Biotech and the data will also be made available to the global research community.

Advancing research and technological innovation

As the largest European charitable funder of Parkinson’s research, the funding from Parkinson’s UK has led to significant breakthroughs, including new drug treatments and non-drug approaches to improve patient lives.

Progress is also being made in the field of diagnostics, with the development of a new potential diagnostic test for Parkinson’s using spinal fluid to detect alpha-synuclein (SAA) markers. The test has shown high accuracy in differentiating Parkinson’s patients from healthy controls, opening up the possibility of using peripheral skin biopsies and blood tests for this diagnostic test, though further replication is currently needed.

Additionally, mitochondrial research has seen recent advances in the area of Parkinson’s disease, which looks at boosting energy production in cells and clearing faulty mitochondria – as mitochondrial dysfunction plays a major role in the condition.

“We have seen a big move in the past decade towards actually looking at individual symptoms of Parkinson’s and how to overcome those, but also looking at how things could slow or stop the progression of the condition,” says Fletcher.

“So that’s underpinned by better understanding of the condition, but we are also looking at and moving forward the development of drugs into areas such as mitochondrial research looking at the cell batteries. We know that these aren’t functioning as well as they should be in Parkinson’s, so this is one target that I think the research really has propelled forward.”

A Phase I first-in-human clinical trial, funded by the Parkinson’s UK Virtual Biotech and Mission Therapeutics, is now underway to test the drug MTX325 which targets mitochondrial dysfunction in the condition. The trial is evaluating the safety, tolerability, pharmacokinetics and brain penetration of the drug. Further to mitochondrial research, recent trials have shown the potential of GLP-1 receptor agonists in slowing disease progression, with phase III trial readouts expected in the near future.

Parkinson’s UK is also funding research into non-drug treatments spurred by innovations in technology. One such innovation is a new research initiative at the University of Nottingham, investigating a wearable wrist device to help control Parkinson’s associated tremours.

Previous research on the device has shown it is safe and effective for treating involuntary movements associated with Tourette’s Syndrome.

“The wristwear device provides electric, low level electrical stimulation rhythmically to stimulate nerve cells,” says Fletcher.

“It can make changes in the brain that might modulate some of the symptoms of Parkinson’s.

“There are other examples of how technology is innovating treatment approaches, such as looking at ways to deliver speech therapy or physiotherapy using virtual reality and augmented reality, to find better ways of encouraging people to stay active or manage specific symptoms.

“These kinds of non-drug approaches are really exciting because they are novel ways of developing solutions for the community that don’t take as long as looking at potential drug treatments.”

The gut-brain connection

One of the major new insights into the development of Parkinson’s is the understanding that for some patients, the condition may begin in the gut rather than the brain.

This gut-first hypothesis of Parkinson’s disease suggests that people with a history of gastrointestinal problems are more likely to go on to develop the condition, and many patients with the condition experience gastrointestinal problems.

Parkinson’s UK is funding research in this area. One avenue of investigation is looking at probiotics to boost good bacteria in the gut to see if that could impact symptoms in people with Parkinson’s.

Fletcher says: “There’s more and more interest in the links between the gut and the brain in wider health research, but also in Parkinson’s.

“So far, there’s some evidence to suggest that probiotics might help.

“We have also funded research in Edinburgh investigating exactly what changes and what gut bacteria are changing in Parkinson’s, to see if we can modulate those levels to help improve symptoms of the condition.

“The research has so far identified a specific bacteria, Bacillus subtilis, that seems to be changing in Parkinson’s, and the research is trying to find ways to boost that again, through the use of probiotics, but also trying to understand how it all impacts on Alpha synuclein, which clumps together and causes problems.

“It might be forming in the gut before it reaches people’s brains.

“What the research is trying to understand is how this protein might be moving from the gut to the brain, using mouse models.”

CBD for Parkinson’s disease

In recent years there has been an explosion of research into cannabinoids – the compounds found in the cannabis sativa plant.

With increasing evidence showing its effectiveness for conditions such as epilepsy, cannabis based medicinal products (CBMPs) are now available on the NHS in the UK, and some research has now pointed to its potential benefit for managing Parkinson’s symptoms.

One clinical trial, funded by the Parkinson’s UK Virtual Biotech, is looking at cannabinoids – specifically cannabidiol (CBD) – for the treatment of Parkinson’s associated hallucinations.

“The research we are funding in this area is looking at CBD to see if it can help Parkinson’s associated hallucinations and delusions,” says Fletcher.

“They have done the dose finding, and now the research is at the stage where they are looking at 120 people with Parkinson’s and doing a placebo controlled study to see if this helps with Parkinson’s associated delusions.

“More widely than that, they will get a better understanding of how CBD impacts other symptoms of Parkinson’s such as tremours, for instance, and other symptoms associated with the condition.” The trial is currently in the process of recruiting 120 people with Parkinson’s at sites across the UK.

“From our point of view as a researcher, we feel like there’s a gap in the evidence, and that’s why we think this trial in particular is really important and really exciting to start building the case and the evidence for CBD,” adds Fletcher. “And to open the door to more research in the area, because it looks like there could be promise in it.”

Looking to the future

Parkinson’s disease is a complex condition and huge challenges remain in the search for treatments. Parkinson’s UK, however, is hopeful advances will now start to gather momentum through its funding and research initiatives.

“It’s about grouping people into categories or subgroups of the condition, and breaking that complexity down to have real impact for people and developing better ways to manage the condition, as well as diagnosing people earlier to really make sure the research is having the best chance of success,” says Fletcher.

“I think we can say momentum is gathering now, because the tools are being put in place, and we now have biomarker approaches to better measure the success of these potential treatments coming through – and global collaborations are underpinning it.

“It is now going to be more standardised across the board of Parkinson’s research. So, I think it’s really exciting, but this is a huge challenge, and I think one that’s not going to come overnight.

“I think a cure will look different for different people, and I think there’s going to be many things that will impact people with Parkinson’s – what will change one person’s life might not change someone else’s.

“It comes back to breaking down the symptoms and the progression models of different groups of people with Parkinson’s experience, and really making sure everyone is on the agenda too.

“A big challenge across health research is that there’s a lot of ethnic diversity, so how can we make sure that everything that’s being done is underpinned by an understanding of everyone that Parkinson’s impacts – whether that’s gender or ethnic diversity.

“That is something else that I think we need to bring in as we work towards a cure and better treatments for the condition. The complexity and variation is not new, and it’s still a challenge, but I think there is momentum gathering to overcome it, and really make sure there are answers to some of the big questions.” •