This preclinical study will compare the effectiveness of 100 drugs previously evaluated by our iLCT committee to better prioritise the most promising compounds for clinical trial.
About the study
Prof Heather Mortiboys at the University of Sheffield will be conducting a two-year pre-clinical study which aims to assess and compare the efficacy (effect) of 100 iLCT-evaluated compounds in patient-derived dopamine neurons. Created by Cure Parkinson’s, in collaboration with Van Andel Institute (VAI), the International Linked Clinical Trials (iLCT) programme is a committee of 20-30 of the world’s leading Parkinson’s experts who gather annually to review and rank potentially disease-modifying drugs for Parkinson’s. This screening study seeks to better prioritise the most promising iLCT-evaluated drugs for clinical trial and gather some of the remaining evidence necessary to progress these compounds.
To assess this, the project has two key objectives. First, Prof Mortiboys will be looking to determine whether these compounds impact three drivers of Parkinson’s progression. These compounds will be tested in two batches: 50 in the first instance followed by a data review and the second 50 if not enough compounds are showing promising results. The first 50 will be determined by their iLCT rankings. The second objective will be to test some of the compounds in combination to determine whether they have a stronger effect when used alongside a second drug. The compounds will be selected based on the data from the first part of the study and the mechanisms of the drugs.
Trial overview
- Researcher: Professor Heather Mortiboys
- Institution: University of Sheffield
- Project Type: Preclinical
- Status: Active
- Start Date: October 2024
More about the study
What is the cell model being used?
In this study, Prof Mortiboys is using a new cell model to screen a series of iLCT-evaluated drugs. All drugs will be screened in the same laboratory model, allowing for a direct comparison of how they are protecting neurons. The model that Prof Mortiboys uses are directly derived from people with Parkinson’s. Briefly, they take a small skin biopsy (sample) from the forearm of donors (PwP and healthy controls) and reprogramme them into a type of stem cell called an induced neuronal progenitor cell. Stem cells are special human cells that have the ability to develop into other types of cells; in this instance, these stem cells can only become cells found in the brain. From here, over the course of one month, the team in Sheffield are able to produce dopamine neurones. Once these neurons have differentiated, the team can treat for a pre-determined length of time at different concentrations and assess any differences in the mitochondria, lysosomes and alpha-synuclein parameters.
This model has advantages over a different, but similar model, because during the reprogramming phase, the stem cells don’t pass through an embryonic state. This means that they retain characteristics of ageing that people accumulate over the course of their life. This system could be more representative than traditional preclinical models as the cells come directly from people with Parkinson’s.
Video presentation – Dr Francesco Capriglia, University of Sheffield, presenting a poster on the study
Prioritising the most promising drugs for Parkinson’s: our new drug screening project
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