USH1b is a syndrome characterized by inherited, usually congenital deafness, followed by progressive retinal degeneration. Despite the severity of the disease, there is currently no cure. In order to define the best course for treatment of USH1b, it is essential to define the disease mechanism of USH1b in human cells. This is particularly important, since mouse models for USH1b do not undergo retinal degeneration. In these studies, we will perform phenotypic characterization of human cell models for USH1b. In the process, we will test novel hypotheses about MYO7A function in the primary cilium. We will use the phenotypic characterization from our knockout studies in order to test the efficacy of gene replacement using cDNA containing either of the two dominant splice isoforms of MYO7A. Taken together, this project is expected to provide important biological insights, as well as urgently important preclinical knowledge.
MYO7A is a motor molecule expressed in all cilia, which is essential for the senses of vision and sight. Our first goal is to understand the function of MYO7A and the disease mechanism of USH1b, caused by mutations in MYO7A. Our second goal is to use this functional information to define the optimal course for gene therapy in USH1b patients.
|Williams, D S; Chadha, A; Hazim, R et al. (2017) Gene therapy approaches for prevention of retinal degeneration in Usher syndrome. Gene Ther 24:68-71|