Development of pharmacological correctors for Alpha-1 antitrypsin deficiency (ATD) using VIPER

Challenge: Drug discovery by high-throughput screening of candidate compounds is usually limited in efficacy as their functional potential is not assessed in relevant biological systems, such as patient cells, during this first selection; new platforms are needed that enable functional testing within specific biological systems. An example of protein trafficking that would benefit from such platforms is Alpha-1 antitrypsin deficiency (ATD)an orphan disease, whose behaviour in the endoplasmic reticulum (ER) is complexrendering the design of therapeutic candidates difficult.

Solution: The primary goal of this project is to validate the utility of IPPERa platform developed within a collaboration funded by CQDM through the Quebec-Germany program between Pr. Thomas (McGill) and LDC (Germany), in drug discovery of therapeutics for protein trafficking diseases, in particular for Alpha-1 Antitrypsin Deficiency. This challenge is an excellent opportunity to show the power of IPPER to resolve a major problem in cell-based high throughput screening. The team will validate VIPER reporter platform, an enhanced version of IPPER platform, as a versatile tool to aid the development of novel therapies, while providing additional tools, standard operating procedures and lead compounds to correct ATD. More specifically, the project will lead to the identification of candidate moleculespreselected by their ability to activate the Alpha-1 antitrypsin pathwaythe validation of these candidate compounds and the elucidation of their mechanism of action.

Achievements/Impact: Beside the major benefits associated with the discovery of new compounds of interest for ATD patients, a critical achievement is the availability of a patient cell-based platform that can identify drug candidates with therapeutic potential in specific cellular systems, such as endoplasmic reticulum-associated  will be offered as a technical service for the team’s in-house projects, for pharmaceutical companies and contract research organizations. This proof-of-principle project will allow Traffick Therapeutics (TTI), a Montréal-based R&D company with expertise in translational respiratory disease research, to attract new investors and further expand its development. In addition, this project will strengthen partnerships between several internationally-renowned institutes.

Principal Investigator:

David Y. Thomas
McGill University


John Hanrahan 
Traffick Therapeutics 

Eric Chevet 
INSERM (France) 

Bert Klebl 
Lead Discovery Center (Germany) 

Ongoing Project
$2,027,577 / 3 years


Supported by CQDM through:
• Pfizer Canada

And by co-funding partners:
• Traffick Therapeutics
• Lead Discovery Center