Lawrence Lustig, MD, Professor at Columbia University Medical Center, discusses early results from the CHORD clinical trial testing gene therapy to treat otoferlin-related hearing loss.
Otoferlin (OTOF)-related hearing loss is a rare genetic auditory synaptopathy that results from defective synaptic transmission from normally functioning cochlear inner hair cells to the auditory nerve. The condition typically results in deafness at birth and current management involves cochlear implants.
DB-OTO is a virally mediated dual adeno-associated virus 1(AAV1) gene therapy that delivers human OTOF complementary DNA regulated by a hair-cell specific promoter. By restoring normal otoferlin function the therapy has the potential to also restore hearing.
The CHORD clinical trial (NCT05788536) is an investigational phase 1/2, open-label, multicenter study evaluating the safety, efficacy, and tolerability of DB-OTO in children and infants with biallelic OTOF mutations. Data was recently presented from an open-label, single-group, first-in-human registrational study of 12 patients treated with DB-OTO.
After a single infusion of DB-OTO, a pure-tone audiometry average threshold of 70 dB hearing level or less at week 24 and an auditory brain-stem response at or below 90 dB normalized hearing level was found in 75% of patients. Six of these patients were able to hear soft speech without assistive devices, and 3 had average normal hearing sensitivity. A total of 67 adverse events were reported but none led to discontinuation of treatment.
Dr. Lustig explains that next steps include evaluating DB-OTO in a larger patient cohort and following those already enrolled for long-term data and results.
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To learn more about OTOF-related hearing loss and other rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/