Unmet Need
The development of new drugs is a capital and time intensive process. For this reason, the development of orphan drugs for those diseases that affect a small subset of the population. One of such diseases, Duchenne’s muscular dystrophy (DMD) affects 1 in 5000 boys worldwide and has no known cure. Current drug screen platforms include animal models and myoblasts from patient biopsies which each have their challenges, including failure to translate to human treatments and limited phenotypical diversity, respectively. Thus, there is a need for a high throughput and efficient drug screening platform to search for cures.
Technology Overview
A drug screening system involving DMD human induced pluripotent stem cells (DMD-hiPSCs) and high content imaging has been developed. One in-vitro proxy for DMD is deficiency in myoblast differentiation and fusion. Using this characteristic, DMD-hiPSCs are differentiated in an extracellular matrix and purified for myoblasts using a unique cell surface marker. Once myoblasts are plated, various compounds can be tested in-vitro for their effect on differentiation and fusion by high content imaging. This platform was tested using 1,524 small molecule compounds from the Johns Hopkins Clinical Compound Library, where 9 compounds produced significant increases in in-vitro fusion rates. Two compounds were selected for an in-vivo mouse DMD model study, where both significantly ameliorated DMD skeletal muscle disease phenotypes. This platform demonstrates the feasibility of early-stage drug development for rare and neglected diseases using symptom-relevant cells derived from patient-specific hiPSCs.
Stage of Development
The inventors have developed an in-vitro drug screening platform for DMD using hiPSCs. The platform was tested on 1,524 compounds and 2 selected compounds were shown to improve DMD symptoms in an in-vivo model.
