Considering gene therapy to protect from X‐linked deafness DFNX2 and associated neurodevelopmental disorders

Mutations and deletions in the gene or upstream of encoding POU3F4 transcription factor cause X-linked progressive deafness DFNX2 additional neurodevelopmental disorders humans. Hearing loss can be purely sensorineural mixed, that is, with both conductive components. Affected males show anatomical abnormalities inner ear, which are jointly defined as incomplete partition type III. Current approaches to improve hearing speech skills patients do not seem fully effective. Owing ear malformations, cochlear implantation is surgically difficult may predispose towards severe complications. Even cases where safely performed, outcomes remain highly variable among patients. Mouse models for revealed could arise from a dysfunction spiral ligament fibrocytes lateral wall cochlea, leads reduced endocochlear potential. Highly positive potential critical sensory hair cell mechanotransduction hearing. In this context, here, we propose develop therapeutic approach male Pou3f4−/y mice based on an adeno-associated viral (AAV) vector-mediated transfer fibrocytes. Among broad range AAV vectors, AAV7 was found strong tropism ligament. Thus, suggest AAV7-mediated delivery Pou3f4 complementary DNA represent attractive strategy prevent fibrocyte degeneration restore normal functions properties, including potential, before progresses profound deafness.