High Content Discovery Assay for Muscular Dystrophy Therapeutics

DESCRIPTION (provided by applicant): Muscular Dystrophy (MD) refers to a group of genetic disorders that cause progressive loss of strength in skeletal muscle leading to varying degrees of disability and, often, premature death. Duschenne's MD is both the most common and one of the most severe of these diseases affecting approximately 1 in 3,500 males and is caused by abnormalities in the gene encoding dystrophin. There are currently no specific treatments for MD. Discovery of novel therapeutics for MD is inhibited by a lack of adequate disease models that are amenable to either high-throughput or high-content screens. The zebrafish, Danio rerio, has become widely accepted as a model for human disease. It is genetically and anatomically similar to other vertebrates, and its external development and optical transparency greatly facilitate real time observation of its internal organs. Zebrafish models for a number of MDs have been developed and show great promise for chemical library screening. In Phase I, PSI plans to develop a high-content, moderate throughput, quantitative, image-based, drug discovery assay using zebrafish MD models in combination with PSI's SideView microplate technology. In Phase II: reagents and consumables will be validated and automated image analysis tools will be developed; and a compound library screen will be performed. PUBLIC HEALTH RELEVANCE: The Phase I and Phase II programs will develop a fully automated tool for discovery of potential therapeutic compounds that reverse the muscle damage caused by Muscular Dystrophy. The assay will be performed in zebrafish larvae which will result in a higher probability that identified compounds will proceed through the drug development process.