Development of a Drug Discovery Platform for Human Islets

DESCRIPTION (provided by applicant): Diabetes and diabetes-related co-morbidities are at epidemic proportions and an enormous burden to our healthcare system. Although there has been significant progress in defining the causative factors and molecular mechanisms involved in both type 1 and type 2 diabetes, it remains an overwhelming challenge to identify efficacious therapeutic modalities. Novel approaches and tools to accelerate research and development of additional therapeutics are urgently needed. Although the mechanisms are distinct, in both type 1 and type 2 diabetes there is a loss of pancreatic islet resident ?-cells or??-cell function, resulting in a complete or significant reduction in insulin production. Human islets are currently the most physiologically relevant system for the validation of potential therapies that modulate the metabolic regulation of insulin production and factors that regulate growth, differentiation, and apoptosis of??-cells. Biotech and pharmaceutical companies are in urgentneed of novel approaches and tools to accelerate their drug development programs that require human islets and islet-derived cells. ZenBio has recently launched a human islet program in which we are obtaining human islets from Prodo Labs and are offering islet cell-based assays in low throughput platforms. We have received numerous requests for cell based contract research services utilizing both human and porcine islets and islet-derived cells. In our discussions with these companies it became evident thathigher throughput platforms using human islets were essentially non- existent, yet highly desirable. In this application we propose to establish cGLP-assays through adapting human islets and islet-derived ?-cells to a robust, reproducible and validated high throughput screening platform. This strategy will allow ZenBio to increase screening capacity in an efficient and reliable format providing a much needed accelerant in diabetes drug discovery. We foresee a significant commercial opportunity for the company in providing these services. PUBLIC HEALTH RELEVANCE: Diabetes is a significant worldwide healthcare problem. Novel tools and approaches are urgently needed in effort to accelerate development of therapies to treat diabetes. This proposal describes a plan to adapt human islets and islet-derived cells to high throughput drug screening platforms; and integrate these assays to our current suite of contract research capabilities.