Pre-clinical development of a lentiviral gene therapy to treat hearing and balance loss in Usher 1B patients

Introduction

The most prevalent genetic sensory defect, sensorineural hearing loss (SNHL), affects over 430 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 Basis of SNHL

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 is an especially severe form of SNHL, with loss of vision and balance accompanying the profound deafness.

Challenges in Gene Therapy

The size of the underlying genes, mutations of which are causative for Usher syndrome, exceeds the cargo capacity of gene therapy vectors currently employed to treat inner ear disorders.

Project Overview

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 beyond state-of-the-art lentiviral vectors (LV). As these LV have the capacity to deliver large genetic payloads, we acquired initial data demonstrating functional improvement in a knock-out mouse hearing loss model following LV application.

Objectives of MY(O)SENSES PoC Proposal

The MY(O)SENSES PoC proposal aims to advance these valuable research results towards clinical application by:

1. Completing pre-clinical development
2. Securing IP rights
3. Commercializing a formulated medicinal product to launch a first-in-human clinical LV gene therapy trial to treat Usher syndrome patients

Potential Impact

This ground-breaking concept can be extended to treat late-onset hearing loss in patients with heterozygous mutations and can be transferred to similar diseases with a genetic or acquired cause. The MY(O)SENSES product will be the first and only treatment that addresses the debilitating vertigo in combination with treating hearing loss in Usher syndrome patients, having the potential to drastically improve patients' lives and benefit society.