The most prevalent genetic sensory defect, sensorineural hearing loss (SNHL), affects 360 million people and results in substantial financial and social consequences. Current treatment options are limited, achieving only temporary or partial relief and are restricted to a sub-group of patients. Therefore, novel treatment options are of high clinical need. Genetic mutations play a role in the majority of SNHL cases, which makes SNHL an ideal setting for innovative clinical gene therapy approaches.
Usher syndrome type 1B (USH1B) is an especially severe form of SNHL, with loss of vision and balance accompanying the profound deafness. The size of some genes, mutations of which are causative for USH1B, exceeds the cargo capacity of gene therapy vectors currently employed to treat inner ear disorders. In my ERC-funded consolidator project "iHEAR", we have provided the first ground-breaking evidence of efficient gene transfer into inner ear cell types using lentiviral vectors (LV). As these LV have the capacity to deliver large genetic payloads, we acquired initial data demonstrating functional improvement of balance and hearing defects in a knock-out mouse model following LV application. This MY(O)SENSES PoC proposal aimed to advance these valuable research results towards clinical application by completing pre-clinical development and securing the exploratory pathway to form the basis for a later first-in-human clinical LV gene therapy trial to treat USH1B patients. The results obtained in this PoC grant will, moreover, help to extend this concept to treat inherited and acquired hearing loss in patients. In particular, the The MY(O)SENSES gene therapy approach will be the first and only treatment to address debilitating vertigo and hearing loss, thus, addressing 2 major senses. This will have major impact with the potential to drastically improve patients’ life and benefit society.
