Z-BRAIN: A Zebrafish Drug Screening Platform Targeting Brain Disorders

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.