Development of allele-specific CRISPR-nuclease gene therapy for late-onset sensorineural hearing impairment in a new humanized DFNA9 mouse model.

Hearing impairment is the most frequent sensory deficit in the human population, affecting 440 million people worldwide, whereby loss of hearing and balance has a significant impact on quality of life and society. Hearing loss is also listed by the World Health Organization as a priority disease for research into therapeutic interventions to address public health needs. DFNA9 (DeaFNess Autosomal 9) is an autosomal dominant hearing disorder caused by a heterozygous gain-of-function mutation in the COCH gene (Coagulation Factor C Homology) and is characterized by progressive late-onset (3rd-5th decade) sensorineural hearing loss (SNHL) and deafness. At current, it is believed that the presence of aberrant COCH proteins in the extracellular matrix (ECM) of the inner ear leads to local cell damage resulting in progressive hearing loss. Within Belgium and the Netherlands, there are > 1000 patients affected by the P51S COCH mutation, who – in the current absence of a disease modifying therapy – will develop deafness and balance loss. Furthermore, there are over twenty different COCH mutations identified in people from all over the world that lead to SNHL. Given the genetic nature of this disorder with highly specific mutations, as well as recent advances in CRISPR-nuclease mediated gene therapeutic approaches, there is a great opportunity to develop a successful therapeutic strategy to reduce or prevent DFNA9-induced SNHL.

Keywords:DFNA9, VESTIBULAR HYPOFUNCTION, HEARING LOSS, GENE THERAPY

Disciplines:Genetics, Otology

Project type:Collaboration project