In this grant application we propose to investigate potential treatments for a currently incurable and particularly tragic type of retinal degenerative blindness: retinal degeneration caused by CLN3-associated Juvenile Neuronal Ceroid Lipofuscinosis. CLN3 disease is an autosomal recessive neurodegenerative disorder mainly affecting children that leads to severe central nervous system degeneration that includes onset of seizures, motor deficits, cognitive regression, loss of vision, and early death. In this research proposal we will use patient-specific induced pluripotent stem cell (iPSC) derived retinal neurons from molecularly confirmed patients with CLN3-associated JNCL as a human model system for evaluating the therapeutic efficacy of pharmacologic compounds via a high throughput drug screen. Our experiments will pave the way for development of novel drug-based treatments.
CLN3-associated Juvenile Neuronal Ceroid Lipofuscinosis is a devastating disease of childhood that involves early onset blindness, seizures, motor deficit, congnitive decline and severe degeneration of the central nervous system. Currently there is no treatment or cure for this condition. We propose multidisciplinary experiments using patient-specific induced pluripotent stem cells and stem cell-derived retinal neurons to explore perform high throughput drug screening to identify novel treatments for this devastating disorder.