Positive Preliminary Results for Gene Therapy in Auditory Neuropathy Spectrum Disorder

Описание: Lawrence Lustig, MD, Otolaryngology-Head & Neck Surgery at Columbia University, discusses preliminary results from the CHORD trial testing the safety, efficacy, and tolerability of investigational gene therapy, DB-OTO, in children with otoferlin-related auditory neuropathy.

Auditory neuropathy spectrum disorder (ANSD) is a rare condition that can affect a person's ability to hear. Although sounds enter the inner ear normally, signals from the inner ear to the brain are not transmitted properly. As a result, the condition may be associated with mild to severe hearing loss and poor speech-perception abilities. The exact cause of ANSD is not completely understood, with over 100 different gene mutations being linked to genetic deafness. Otoferlin-related hearing loss is caused by mutations in the otoferlin gene, which impairs the production of OTOF protein. This protein plays an important role in the communication between sensory cells of the inner ear and the auditory nerve. Current management for these patients include hearing aids and cochlear implants.

DB-OTO is an investigational adeno-associated virus (AAV) gene therapy in development for children with profound genetic hearing loss caused by otoferlin gene mutations.

The CHORD clinical trial is an ongoing Phase 1/2 first-in-human, multicenter, open-label study evaluating the safety, efficacy, and tolerability of DB-OTO in children with otoferlin-related ANSD. Preliminary results were presented at the American Society of Gene and Cell Therapy (ASGCT) annual conference.

The first patient dosed in the trial showed improvement of hearing to normal levels and positive auditory brainstem responses at the 24-week assessment, at which point the patient was 16 months of age. Additionally, the second patient, age 4, showed initial improvement of hearing with responses to loud sounds and positive auditory brainstem responses at the 6-week assessment. Positive safety and tolerability measures have also been observed.

Chapters:
Intro 00:00
Genetic Deafness Overview 00:16
Current Management 4:50
DB-OTO Gene Therapy 5:50
CHORD Trial Overview 7:08
Next Steps 10:54