Using zebrafish models of rare diseases to accelerate orphan drug discovery

Only a small minority of the estimated 7,000 rare diseases have an approved drug, creating the urgent need for new approaches to accelerate orphan drug development. Zebrafish are a powerful model organism, ideally suited for the rapid generation of biomedically relevant and predictive in vivo bioassays for a wide range of human genetic diseases. Because of the small size of their embryos and larvae with which most bioassays are developed, zebrafish models of human diseases enable the high-throughput, microscale in vivo screening of small molecule libraries. Zebrafish have therefore emerged as a promising tool for modeling rare diseases and supporting orphan drug discovery. In my presentation, I will review how we and others are using zebrafish to model rare diseases, and will highlight our recent progress in using genetically-modified zebrafish models to identify new orphan drug candidates. The need to expedite orphan drug development has created an urgency for identifying new uses for existing drugs (drug repurposing). As a result, the development of animal models able to support the screening of approved libraries of compounds in multiple rare disease-relevant assays has become a key priority and a limiting step in the development of orphan drugs. As the field of medicine moves towards more patient-specific models and shorter development timelines, zebrafish are rapidly becoming a key drug discovery tool with the potential to revolutionize not only orphan drug discovery but also personalized medicine.