Zebrafish Muscular Dystrophy Model for Drug Screening

DESCRIPTION (provided by applicant): This SBIR proposal aims to develop and validate a zebrafish model for screening drugs that mitigate symptoms associated with muscular dystrophy (MD). MD is comprised of several clinically and genetically heterogeneous disorders characterized by progressive weakness and degeneration of the skeletal or voluntary muscles which control movement. In some forms of MD, heart muscles and some involuntary muscles are also affected. MD can occur at any age. Duchenne is the most common form of MD affecting children, whereas myotonic is the most common form affecting adults. Although there has been tremendous improvement in the understanding of the molecular basis of MD, no effective treatment is currently available. Development of therapeutic strategies is a major focus of the biopharmaceutical industry. Murine and canine models have been useful in elucidating MD disease mechanisms and assessing potential therapeutic strategies, but neither model can be used for large scale genetic screens or for rapid drug screening. Although simpler in vivo model systems such as C. elegans (dys-1) have been developed, these invertebrate models are relatively poor predictors of efficacy and toxicity in humans because their metabolism and physiology are very different from those of humans. A new animal model that combines the advantages of invertebrate and mouse systems is needed to streamline the drug discovery process. This zebrafish model will facilitate screening of potential therapeutics that mitigate symptoms associated with muscular dystrophy and streamline the drug development timeline.