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

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

Competition: Focus on Brain 2015
Funding: $1,500,000 / 3 years
in collaboration with Brain Canada
Beginning: November 2016

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. With Canada’s aging population, and without any current efficacious treatments for these diseases, it is imperative to develop new therapies.

A major roadblock to new drug development in neuroscience has been the limited access to human neurons from affected patients. Such limitation has now been addressed through the identification of specific factors allowing the transformation of skin or blood cells from any individual, into stem cells known as induced pluripotent stem cells (iPSCs). In appropriate culture conditions, these iPSCs can become different types of neurons, thus allowing diseases such as PD and ALS to be modeled, studied and interrogated in a dish.

The research team will harness the power of iPSCs to develop a first-in-kind drug discovery platform to identify new drugs against PD and ALS. In addition to cell lines derived from healthy individuals, they will generate 24 cell lines from both PD and ALS patients, including 12 derived from patients harboring sporadic diseases and 12 others involving known genetic mutations. To assess the effects of putative drugs on these neurons, three different disease-relevant assays will be developed for PD: synuclein propagation, mitochondrial turnover, and GBA1 activity and lysosomal function. Three more specific assays will also be developed for ALS: SOD1 uptake and propagation, TDP43 and FUS1 misfolding, and mitochondrial turnover. To further accelerate the development of new medications against these diseases, all cell lines and assay protocols will be put in the public domain for scientists to use them. Moreover, the proposed approach could also be easily applied to other neurological diseases such as multiple sclerosis, dementia and neuropsychiatric disorders.