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Enhancing the efficacy of heat shock protein inducers by cotreatment with a histone deacetylase inhibitor – A therapeutic strategy for ALS

Principal Investigator:
  • Heather Durham, McGill University
Team Members:
  • Chantelle Sephton, Université Laval
  • Richard Robitaille, Université de Montréal
  • Josephine Nalbantoglu, McGill University
  • ALS Society of Canada

Project Overview

In ALS and many other neurodegenerative diseases, one of the defining characteristics is that proteins can become misfolded and clump together, potentially damaging nerve cells. When a healthy body responds to stress, protective mechanisms increase the production of heat shock proteins that help prevent protein misfolding. This mechanism can become impaired when healthy motor neurons are compromised by disease processes. For years, Dr. Durham has been studying drugs that might enhance heat shock protein response in motor neurons. Recently, she has found a particular drug combination that can greatly increase the production of heat shock proteins in motor neurons.

This project sets the stage for researching a promising drug combination that may one day become an important therapy for people with ALS. Dr. Durham and collaborating researchers Dr. Josephine Nalbantoglu, Dr. Richard Robitaille, and Dr. Chantelle Sephton will seek to find the optimal combination of heat shock drugs together with a histone deacetylase drug and then examine the protective capabilities of the best combination in ALS mice. They will also investigate how the drugs work, which could lead to the development of potential biomarkers for human clinical trials in the future. The team will collaborate with multiple biotech and pharmaceutical companies that own the unique heat shock and histone deacetylase drugs. If this project is successful, the next step would be for drug companies to conduct toxicity testing and ultimately clinical trials with human volunteers.

Summary from ALS Canada: