STTR Phase I: Human Microphysiological Model for Assaying the Efficacy of Drugs for Myelin Disorders

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) project is to develop a commercially-viable human cell-based model to screen experimental drugs for their efficacy in treating myelin disorders. Current screening methods used in the R&D of new drugs fail to successfully predict translation from discovery to clinical success. This absence results in high attrition rates, increased development time, and significant R&D costs, most acutely in neurological applications. Pharmaceutical companies devote up to 15 years and spend over $2B to bring a single drug to market. On average, 89% of drugs entering clinical trials fail, while drugs targeting the central nervous system (CNS) fail at a rate of 92%, due largely to the poor predictive validity of current animal models. As a case study of demyelinating diseases, multiple sclerosis (MS) affects approximately 400,000 people in the United States and 2.5 million people worldwide. MS therapeutics represent a $17.2B global market, with an estimated late-stage preclinical testing market of $50M annually. Development of the proposed screening platform has the potential to better predict clinical efficacy, while substantially reducing the time and cost associated with developing new drugs for MS and other demyelinating disorders, accelerating treatments for millions of patients. This STTR Phase I project proposes to establish the technical feasibility of using a 3D model of living nerve/brain tissue for screening drugs to treat disorders of myelin, the fatty encasement surrounding nerve axons. The project aims to build on preliminary work to include cells relevant to the central nervous system. It will then be shown that myelination, demyelination, and remyelination can be assessed using clinically-relevant, physiological metrics. The final goal is to demonstrate the feasibility of using a humanized assay, derived from induced pluripotent stem cells, a renewable source of human cells. The resultant model system will be truly unique, comprised of human cells in an anatomical arrangement that mimics living nerve tissue, unlocking the potential for clinically-relevant metrics far earlier in the drug development lifecycle.