Advancing gene therapy to address deafness

Irvine, Calif., July 20, 2025 — 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,” he says. “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.”

About the UC Irvine School of Medicine: Each year, the UC Irvine School of Medicine educates more than 500 medical students and nearly 150 PhD and MS students. More than 750 residents and fellows are trained at the UCI Medical Center and affiliated institutions. The School of Medicine offers multiple MD, PhD and MS degrees, and students are encouraged to pursue an expansive range of interests and options. The UC Irvine School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit medschool.uci.edu.

About the University of California, Irvine: Founded in 1965, UC Irvine is a member of the prestigious Association of American Universities and is ranked among the nation’s top 10 public universities by U.S. News & World Report. The campus has produced five Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UC Irvine has more than 36,000 students and offers 224 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $7 billion annually to the local economy and $8 billion statewide. For more on UC Irvine, visit www.uci.edu.