The International Parkinson’s Linked Clinical Trials (LCT) Initiative

Original article: Brundin, P, Wyse, RK. October 2018. The Linked Clinical Trials Initiative (LCT) for Parkinson’s disease, European Journal of Neuroscience. 

The takeaway

In 2011, the Linked Clinicals Trials (LCT) programme of research was established, with a clear focus on advancing research into cures for Parkinson’s. Each year since then, an international committee of experts convenes to identify drugs with the potential to slow, stop or reverse Parkinson’s.

Why is it important?

LCT is the legacy of Tom Isaacs, co-founder of The Cure Parkinson’s Trust, and now brings together charities, research organisations and experts from around the world. Since the first annual meeting in 2012, over 2000 drugs have been screened for their potential to be repurposed for Parkinson’s. These efforts have been instrumental in bringing directly to trial a number of important drugs with disease modifying potential.

Impact

“This paper provides a wonderful overview of the Linked Clinical Trial initiative, delving deep into the history of the programme and sharing much of the back story. What began as an innovative “thinking outside the box” idea has now become a template that adovacates for many other conditions are emulating. Numerous clinical trials have resulted from the effort, with many more planned. It is certainly an amazing legacy for Tom Isaacs.”

Background

The mission of the LCT is to bring to trial drugs that show promise in terms of stopping, slowing or reversing Parkinson’s. A key aim is that this programme of research should translate ideas into trials with as little delay as possible, in line with the sense of urgency instilled by Tom Isaacs, one of the co-founders of The Cure Parkinson’s Trust.

The details

Each year, a committee of world-class Parkinson’s researchers, including clinicians and scientists, convene to discuss and debate the arguments for a number of drugs, drawing on the LCT dossiers, which contain reports on the rationale and scientific evidence supporting each of the different agents that make it to this shortlist. Spearheading this effort are Dr RK Wyse, director of research and development at The Cure Parkinson’s Trust, headquartered in London, UK, and Dr P Brundin, director of the Center for Neurodegenerative Science at the Van Andel Research Institute, Grand Rapids, MI, USA. People with Parkinson’s, and advocates are also present at these meetings, in the spirit of true stakeholder engagement and collaboration in this huge effort. The committee has so far triaged around 150 candidate drugs over the last 7 years, discussing about 20 drugs each year.

Since 2012, six Phase 2 trials have been launched in the US, UK and France, aiming to address safety and efficacy of the drugs in people with Parkinson’s. Five of these involve drugs that were ranked highly at the very first committee meeting in 2012: these are Bydureon, Liraglutide, Lixisenatide, Deferiprone and Simvastatin. In addition, Nilotinib, which mostly due to unclear safety concerns, was not highly ranked at the 2012 meeting, was discussed again at subsequent LCT meetings and then prioritised and moved forward to trials. Some of these drugs considered by LCT have now also entered independent clinical trials around the world. By mid 2019, it is expected that at least 25 drugs prioritized by LCT will have gone to trial, or reached trial completion. It was originally envisaged that several drugs could be tested in parallel, hence “Linked” trials which might share a single control group or similar protocol, to allow for direct comparison. Now, using innovative trial designs this aspect of the programme is also possible.

LCT is bringing promising disease-modifying therapeutics into long-term neuroprotective clinical trials, because it is (in Tom’s own words) “only through the clinical trial process that we can introduce outstanding therapeutics to the mainstream management of millions of PD patients worldwide”.

Where can I learn more?

Original article: Brundin, P, Wyse, RK. October 2018. The Linked Clinical Trials Initiative (LCT) for Parkinson’s disease, European Journal of Neuroscience. 

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