Principal Investigator
Salah El Mestikawy
Douglas Hospital Research Centre
Project of $3,543,461 over 3 years
- Supported by CQDM through:
Ministère de l’Économie, de l’Innovation et de l’Énergie du Québec (MEIE) - And by co-funding partner:
– Will Therapeutics
The project in detail:
Challenge
Anorexia nervosa affects about 1% of the Canadian population and approximately 8 million women in North America. It has the highest mortality and morbidity rate among all mental illnesses, with 10% of patients dying annually. Despite its profound human and socio-economic impact, no approved, specific, or effective treatment exists. Most patients are treated with neuroleptics and antidepressants that show little to no benefit and the rate of relapse among patients is very high.
Solution
Professor Salah El Mestikawy and his research team at the Douglas Hospital Research Centre identified a key dysfunctional biological and neurochemical system in the brain considered the root cause of habit formation in anorexia. After treating mouse models of anorexia with a drug that alters the balance acetylcholine/dopamine in specific brain areas, they observed a marked reduction of compulsive, self-destructive starvation behaviour. However, severe side effects at required doses were seen, such as cramps, nausea, and diarrhea. To overcome these limitations, the research team designed and developed, in partnership with Will Therapeutics Inc., a series of novel brain-permeant small molecules that can deliver efficacious doses while minimizing peripheral side effects. They have a lead compound that they are currently advancing through animal testing, with hopes of bringing it to the clinic. The primary objective of the project is to advance this lead compound to clinical trials as well as prepare a second backup compound for future trials. The team aims to characterize the pharmacokinetic, safety, and efficacy parameters of the first effective and safe pharmacological treatment for anorexia.
Expected Achievements /Impacts
Their lead compound and its derivatives represent a promising breakthrough in managing people with eating and compulsive disorders. Beyond anorexia, these compounds may also be effective in treating obsessive-compulsive disorder and substance use disorders, with the potential to deliver transformative benefits, including saving lives, improving mental health outcomes, and alleviating societal and economic burdens. Together with the Quebec-based company Will Therapeutics Inc., the team aims to deliver a first-in-class, specific pharmacological treatment for anorexia, positioning Quebec as a leader in neuropsychiatric innovation.
