Abstract

The Clelland lab at UCSF is devoted developing new therapies for neurodegenerative diseases. Age-related neurodegenerative diseases, including dementias, are one of the most medically and economically consequential challenges facing our society. Some dementias clearly arise from mutations in single genes (such as C9orf72), raising the exciting possibility that gene therapy could cure this class of disease. For instance, the most frequent known genetic cause of both frontal temporal dementia (FTD) and ALS, two fatal age-related neurodegenerative diseases, is an expansion of hexanucleotide repeats in the C9orf72 gene. Despite the C9orf72 mutation being present in cells throughout the body from birth, the disease begins in only a subset of aged central nervous system (CNS) cells. With funding from the LHHF, we plan to advance our understanding of how the C9orf72 mutation causes disease using iPSC-derived cells and tissues donated by patients to better model the disease. We will also develop novel CRISPR approaches to correcting the C9orf72 mutation in patient cells.