Project Overview

The traditional target-based drug development strategy (in vitro screening) has had poor success in developing new drugs. The vast majority of Investigational New Drugs (INDs) fail in clinical trials due to toxicity or lack of efficacy. On the other hand, mammalian models are excellent tools to study disease mechanisms and test therapies but are difficult to use for large scale drug screening. Zebrafish has proven to be an ideal preclinical model due to the high percentage of genes associated with human disorders. With support from the Brain Canada platform grant, Dr. wen and his team have built Z-BRAIN, a national high-throughput drug screening platform to target brain disorders, using zebrafish central nervous system (CNS) disease models for direct in vivo drug discovery on zebrafish embryos. This team brings together specialists in drug development, robotic technologies, medicinal chemistry, bioinformatics, disease mechanisms and zebrafish modelling. The brain disorders targeted include, but are not limited to, Alzheimer’s disease, Parkinson’s disease, ALS, epilepsy, schizophrenia, depression/stress, stroke and traumatic brain injury. Six industrial partners (Eli Lilly, Treventis Corporation, Atuka Inc., Edge Therapeutics Inc., Janssen Pharmaceutical, and Life Chemicals) and multiple international collaborators have joined this initiative. The platform is a state-of-the-art system that can perform fully automated screens from fish embryo sorting and drug dosing to efficacy readouts. The Brain Canada funds have been used to hire new research staff to conduct computer and mechanical engineering work associated with the platform, as well as to hire staff for disease modelling, compound screening, drug database development and chemical informatics.

Principal Investigator

Xiao-Yan Wen , St. Michael’s Hospital

Team Members

Pierre Drapeau, CHUM Research Centre, University of Montréal

Raymond Andersen, University of British Columbia

Robert Gerlai, University of Toronto

Georg Zoidl, York University

Loch Macdonald, St. Michael’s Hospital

Andrew Baker, St. Michael’s Hospital

Albert Wong, Centre for Addiction and Mental Health

Marc Ekker, University of Ottawa

Sidney H. Kennedy, University Health Network

Alan Fine, Dalhousie University

Janice Robertson, University of Toronto

Vince Tropepe, University of Toronto

Henry Krause, University of Toronto

Terry Van Raay, University of Guelph

Tom Schweizer, St. Michael’s Hospital

David Munoz, St. Michael’s Hospital

Corinne Fischer, St. Michael’s Hospital

Thomas Steeve, St. Michael’s Hospital

Ted Allison, University of Alberta

Cheryl Gregory-Evans, University of British Columbia

Claudia dos Santos, St. Michael’s Hospital

Partners and Donors

St Michael's Hospital

University of British Columbia

University Health Network

Eli Lilly Company

York University

Atuka Inc.

Treventis Corp.

Centre for Addiction and Mental Health (CAMH)

CHUM

Life Chemicals, Inc.