Diabetes drug screening platforms using patient pancreatic islet-like cells generated from induced pluripotent stem cells

Project Summary Abstract Diabetes manifests when the body s demand for insulin exceeds the capacity of pancreatic cells to produce and secrete it This can arise due to autoimmune destruction of cells Type I diabetes a combination of insulin resistance and subsequent cell failure Type II diabetes or primary genetic defects that impair cell development and function including maturity onset diabetes of the young MODY and Wolfram Syndrome WS As of approximately million Americans suffered from diabetes resulting in direct medical costs of $ billion National Diabetes Statistics Report In order to meet the needs of this growing patient population top pharmaceutical companies such as Eli Lily AstraZeneca and Novo Nordisk have active diabetes pipelines to identify and test molecules that enhance cell function Unfortunately drug discovery efforts in this space are hampered by the absence of a cell drug screening platform that captures both patient genetics and the complex phenotypes of primary cells To meet this need Regenerative Medical Solutions RMS has pioneered a simple proprietary protocol to produce islet like clusters ILC containing multiple pancreatic endocrine cell types including insulin producing like cells from human induced pluripotent stem cells iPSC RMS has demonstrated that these ILC when derived from healthy donor iPSC capture many of the complex phenotypes of primary cells including expression of key marker genes and robust glucose stimulated insulin secretion In order to demonstrate the utility of the platform for detection of pathologies associated with specific patient genotypes RMS will generate like cells from MODY patients with well characterized mutations in the glucokinase GCK gene and patients with WS caused by mutations in the wolframin gene WSF The ability of ILC harboring these mutations to replicate the well established deficits in cell function seen in the patients will be demonstrated and initial quantities of the cells will be made available to RMS s existing customers In a follow on Phase II proposal like cells from patients with more complex genetics i e Type I and Type II diabetes will be developed for use as high throughput screening platforms for drug discovery Project Narrative Diabetes is a serious health problem in the United States Although many drug companies are working to develop new diabetes medicines their ability to discover new drugs that can treat the disease is hampered by the lack of appropriate research tools This project will develop one of the tools that the drug companies need to successfully find new ways to treat diabetes