Inducible human pluripotent stem cells to better understand and treat Parkinson’s disease and ALS

Challenge: Parkinson’s disease (PD) and Amyotrophic Lateral Sclerosis (ALS) are two of the most common and devastating neurodegenerative diseases, affecting one in 50 Canadians over 65 years old. A major roadblock to new drug development in neuroscience is the limited access to human neurons from affected patients. This limitation is now being addressed through the use of induced pluripotent stem cells (iPSCs). In appropriate culture conditions, these iPSCs can become different types of neurons, thus allowing the study of diseases such as PD and ALS in a dish.

Solution: The research team will harness the power of iPSCs to develop a first-in-kind drug screening platform to identify new drugs against PD and ALS. In addition to cell lines derived from healthy individuals, they will generate 24 neuron-derived cell lines from both PD and ALS patients, including 12 derived from patients harboring sporadic diseases and 12 other involving known genetic mutations. To assess the effects of putative drugs on these neurons, three different disease-relevant assays will be developed for PD: GBA1 activity and lysosomal function, synuclein propagation, and mitochondrial turnover. Three specific assays will also be developed for ALS: SOD1 uptake and propagation, TDP43 and FUS1 misfolding, and mitochondrial turnover.

Expected Achievements/Impact: This project will enable the development of a drug screening platform using stem cell-derived neurons from PD and ALS patients. All generated neuron-derived cell lines and assay protocols will be available in the public domain for scientists to use them. Moreover, the proposed approach could also be applied to other neurological diseases.
The project was instrumental in the decision of Merck and the Centre for Drug Research and Development (CDRD) to establish at the Montreal Neurological Institute (MNI) a world-class high-content screening platform and node, called “NeuroCDRD”, to accelerate the identification of relevant targets and development of new drugs for neurological diseases. So far, 5 hits for Parkinson’s disease have been identified. The project has also attracted the interest of pharmaceutical companies including a follow-on investment from Takeda Pharmaceutical.


































Principal Investigator:

Edward Fon
McGill University


Guy Rouleau,
Thomas Martin Durcan,
Philippe Séguéla

McGill University

Nicolas Dupré
Université Laval

Neil Cashman
University of British Columbia

Ongoing Project
$ 1,500,000 / 3 years
Supported by CQDM through:
• Merck
• Pfizer

And by a co-funding partner:
• Brain Canada