The Manton Center for Orphan Disease Research
Gwenaelle Geleoc, PhD
Rescue of Inner Function in Mouse Models of Usher Syndrome
Usher syndrome (USH) is a devastating incurable rare genetic disorder which leads to deafness and blindness. Three clinical subtypes have been described (type 1, 2 and 3). USH1 is the most severe form with profound deafness and balance deficits at birth and progressive vision loss leading to pre-pubertal blindness. USH1 includes a family of five genes that interact and play important functional roles in the sensory cells of the inner ear and the eye. One of the central players, USH1C encodes a protein called Harmonin, which is located in the sound and balance sensing structures of inner ear sensory cells. For this project I will begin to develop treatment strategies for Usher syndrome. I will use deaf and blind mice that carry that same harmonin mutation found in a large family of USH1C patients. Using a gene therapy approach, I propose to repair the sensory cells of the inner ear by introducing the correct DNA sequence for harmonin. Initially, I will examine the ability of the gene therapy approach to restore sound and balance sensitivity at the cellular level. If successful, I will introduce the gene therapeutics into live mice and attempt to restore hearing and balance function in deaf and dizzy mice.