Cure Parkinson’s is excited to announce funding for a pre-clinical project that aims to test, evaluate and compare drugs that have the potential to slow Parkinson’s progression.
Established by Cure Parkinson’s, in collaboration with Van Andel Institute (VAI), the International Linked Clinical Trials (iLCT) committee meet annually to review, rank and prioritise 15 to 20 drugs based on their potential to modify the progression of Parkinson’s. Since it began in 2012, the committee have reviewed more than 180 drugs. The goal of this programme is to prioritise the most promising drugs for clinical trial and, as of 2023, there have been 21 completed and 20 ongoing trials of iLCT-evaluated agents taking place across the globe and involving more than 4700 people with Parkinson’s.
Whilst the impact of the programme is clear, there is a need to get additional information about some compounds in order to progress them into future clinical trials. Therefore, to help gather further data and to direct more drugs into suitable next stages of development, Professor Heather Mortiboys at the University of Sheffield will be investigating 100 iLCT-evaluated drugs in cell models of Parkinson’s.
What will these drugs be evaluated for?
The researchers will be looking at whether these drugs impact three recognised drivers of Parkinson’s progression: problems with energy production, waste removal, and build-up of the protein alpha-synuclein. By doing so, they also hope to gain a better understanding of how these drugs work. Additionally, all drugs will be screened in the same laboratory model, allowing for a direct comparison of how they are protecting neurons (nerve cells). Combination therapy, or using multiple drugs to treat a single condition, is something that has yet to be done in clinical trials for Parkinson’s. Therefore, the team will also test a number of different agents alongside one another to determine whether this creates a stronger effect. In doing so, we could gain some insight into how this approach could be used moving forward.
How will this work be carried out?
Prof Mortiboys has developed a method for using cells derived from people with Parkinson’s to investigate drugs that may be able to slow progression. She is able to take a small skin biopsy from the forearm of donors and, in the lab, reprogramme these into stem cells – special human cells that have the ability to develop into other types of cells. From here, the team in Sheffield can produce dopamine neurons, the type of cell affected in Parkinson’s. This system could be more representative than traditional preclinical models as the cells come directly from people with Parkinson’s.
Our team has found that these dopamine neurons from people with Parkinson’s show abnormalities in the pathways affected in Parkinson’s without any additional toxins. This is really crucial as the cells are not further artificially modulated. We are super excited about this study testing the iLCT compounds in this model.”
Prof Heather Mortiboys, University of Sheffield
The results of this study aim to de-risk drugs that are candidates for clinical trials by improving our understanding of how they work and who they might be suitable for. This is particularly important in the context of the global effort to set up multi-arm, multi-stage (MAMS) clinical trials, where several drugs are tested in unison. During the trial, drugs are assessed for their efficacy (effect) at pre-specified time points and if found not to reach their target, the drug is replaced with an alternative.
Cure Parkinson’s looks forward to receiving an update on the project in Spring 2025.
