Breakthrough gene therapy reverses genetic deafness across age groups

Using gene therapy to treat hereditary deafness is safe and effective in both children and adults, according to new findings from a multicenter clinical trial.

"Cochlear implantation has been the only treatment for deafness, but it does not address the root cause," says Fan-Gang Zeng, PhD, an esteemed hearing scientist in the Department of Otolaryngology in the UC Irvine School of Medicine, where he's also a Chancellor's professor and director of the Center for Hearing Research. "Gene therapy restores biological hearing while removing the need for electronics and batteries."

Zeng collaborated with an international team of researchers during a first-of-its-kind clinical trial, which included 10 participants between the ages of 1.5 and 23.9 years old. Gene therapy studies have shown promising results in addressing congenital deafness in children, but data in older populations has been lacking.

The findings, published in a paper in Nature Medicine, show gene therapy's potential for fast results in both children and adults, with much of the hearing restoration occurring within one month of drug delivery.

Hearing improved from complete deafness to moderate hearing loss (50 dB HL, pure-tone-average behavioral thresholds) in patients with OTOF gene mutations, a relatively rare form of congenital deafness. (The OTOF gene produces a protein called otoferlin, critical for hearing.) The improvement occurred after patients received adeno-associated virus (AAV)-OTOF gene therapy through the injection of an Anc80L65 capsid into the cochlea with a needle.

Zeng says that the next step is to treat patients with other forms of gene mutations, such as GJB2 (mutations in the gap junction beta-2 protein), noting that hearing loss is the most common sensory defect.

It affects 2 per 1,000 newborns, with 50%-60% of the cases being attributed to genetic factors. Our promising results open doors for not only probing mechanisms underlying the biology of gene therapy, but also treating patients with different hereditary hearing disorders."

 Fan-Gang Zeng, PhD, Department of Otolaryngology, UC Irvine School of Medicine