*PHILIPPE GROS

Exploitation of a new pharmacological target for the development and validation of new anti-inflammatory drugs

Challenge: Neuroinflammation (NI) is involved in a diverse array of degenerative conditions, ranging from multiple sclerosis (MS) to Parkinson’s and Alzheimer’s disease. Although treatment options are available for MS their effectiveness is not uniform and long-term use has significant side effects. NI-based disorders remain an area of high unmet medical need and new approaches and targets are required to find disease-modifying therapies for patients.

Solution: In previous studies, the team had discovered that inactivation of the ubiquitin-specific protease USP15 protects mice against lethal NI in microbial and autoimmune experimental models. The current project successfully developed and validated specific inhibitors of USP15 in view of managing and treating NI. More specifically, USP15 inhibitors of therapeutic value were developed and optimized in potency, selectivity and efficacy in blunting NI in vitro and in vivo in new animal models that were developed as part of the project. Furthermore, the function of USP15 was investigated in different immune cell populations and brain cells and cell-specific biochemical pathways were identified. Finally, a mouse model of PD was developed and can now be used to map out therapeutic applications of USP15 modulators.

Achievements/Impact: Thanks to its three funding partners, Corbin Therapeutics, HBHL and Brain Canada, the project was a success on all fronts. It managed to gain fundamental knowledge on the functional role of USP15 in NI, including the development and validation of USP15-deficient animal models that can benefit the NI research community; to achieve identification of promising therapeutics in the form of small molecule USP15 inhibitors tested in vitro and in vivo, which will be further optimized and validated in preclinical studies; and to develop and validate a Parkinson’s disease mouse model. All these activities were quality-focused and well coordinated in partnership with state-of-the-art laboratories, which positions the drug candidates in a very favorable stage for clinical development by Corbin Therapeutics.

 

 

 

 

 

 

 

 

 

 

 

 

Principal Investigator:


Philippe Gros
McGill University

Co-investigator

Véronique Bougie
Corbin Therapeutics

Completed Project
$ 1,375,000 / 2 years
Supported by CQDM through:
• MEI

And by co-funding partners:
• Corbin Therapeutics
• Healthy Brains, Healthy Lives (HBHL)
• Brain Canada