Drug Repurposing Project
Abstract: Vici syndrome [OMIM242840] is a rare and severe congenital multisystem disorder characterized by a constellation of abnormalities including callosal agenesis, cataracts, cardiomyopathy, hypopigmentation, combined immunodeficiency and variable involvement of other organ systems, including thyroid, lungs and kidneys. Most patients fail to thrive, have acquired microcephaly, and multisystem involvement affecting virtually every organ system. There are no treatment options for these patients resulting in a poor overall prognosis. Using patient-derived fibroblasts deficient in EPG5, we seek to identify drugs and compounds that induce autophagy. Hits identified from our library of FDA-approved and abandoned drugs will not only serve as readily available probes to validate the proposed drug target but may also represent potential therapeutic opportunities that can be accelerated to patients. Hits obtained from our 300,000 compound library serves as the basis for launching a medicinal chemistry campaign designed to generate and optimize small molecule lead candidates.
Vici Syndrome patient advocates have assembled a multidisciplinary, multi-organizational project team comprised of basic and translational researchers at INOVA Translational Medicine Institute (ITMI), Georgetown University, the Coriell Institute for Medical Research, and the University of Kansas fully committed to discovering and developing treatments for these patients. The University of Kansas, home to one of the leading academic, fully integrated drug discovery and development enterprises in the US, is home to a state-of-the-art high throughput screening laboratory that assists researchers throughout the world in identifying biological probes for target validation and drug discovery. Its personnel have extensive experience in executing biochemical, cell-based, siRNA as well as high content screening campaigns against a plethora of target classes.
The Institute for Advancing Medical Innovation (IAMI), headquartered on the University of Kansas Medical Center campus, conducts product development-focused translational research focused on discovering and developing novel agents as well as repurposing FDA-approved and abandoned drugs for the treatment of cancers and rare diseases.Utilizing patient-derived fibroblasts established by Vici Syndrome patient advocates, we will develop a high content imaging assay in which patient and control cells contain a stably expressed reporter. Libraries containing 300,000 compounds as well as FDA-approved and abandoned drugs will be evaluated.