A Drug Screening Platform to Increase Protein Expression Levels for Treatment of Neurological Disorders


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Challenge: Neurological and psychiatric diseases and disorders affect more than half the population, causing a huge burden on health care costs, lost productivity, and reductions in quality of life. These disorders of the nervous system can span a range of illnesses, including autism spectrum disorders, manic disorders, Parkinson’s disease, stress, depression, and anxiety. Many of these diseases and disorders are caused by abnormal levels of protein expression. Thus, there is a need to identify drugs that can re-establish normal protein expression levels, which could result in the reduction of the disease phenotype and slow down of its progression.

Solution: The team will develop a high-throughput drug screening platform to identify molecules that increase the protein expression for specific genes associated with diseases and disorders of the nervous system. The researchers concentrate their efforts on three genes: SHANK3 which is associated with Phelan-McDermid syndrome and autism; GBA1 which is associated with Gaucher’s and Parkinson’s diseases, and SLC6A15 which is associated with stress and anxiety. The team is using their recently developed technology (Protein Quantitation Ratioing (PQR)) to measure protein production of these three genes individually over time in single human cells. To identify drugs that can restore protein levels, the researchers will develop cell assays where protein expression of the gene of interest (SHANK3, GBA1 and SLC6A15) along with a control gene’s protein expression are monitored simultaneously in the presence of different concentration of drugs.

Expected Achievements/Impact: This approach will help generate molecular treatments for any disease or disorder caused by insufficient gene expression, including those involved in autism spectrum disorders, anxiety and depression, and neurodegeneration. By using patient-derived cells, this strategy can also offer a new avenue for individualized and rapid drug discovery for patients with diseases caused by low gene expression. Moreover, screening with FDA approved drug libraries will result in accelerated Phase II clinical trials and faster access of these drugs to patients.

Principal Investigator:
Brian Chen
The Research Institute of
the McGill University Health Centre
Ongoing Project
$ 1,450,000 / 3 years
Supported by CQDM through:
– Pfizer
And by co-funding partners:
– Healthy Brains for Healthy Lives
– Brain Canada Foundation
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