New gene therapy restores hearing in kids with hereditary deafness

Researchers have developed a gene therapy that can help restore hearing function for children suffering from hereditary deafness.

In the first human clinical trial that took place in December 2022, the team from Massachusetts Eye and Ear Infirmary in the US administered gene therapy to six children in China.

The results, now published in the journal The Lancet, found the gene therapy to be an effective treatment for patients with a specific form of autosomal recessive deafness caused by mutations of the OTOF (otoferlin) gene, called DFNB9.

"If children are unable to hear, their brains can develop abnormally without intervention," said Zheng-Yi Chen, Associate Scientist at Mass Eye and Ear.

"The results from this study are truly remarkable. We saw the hearing ability of children improve dramatically week by week, as well as the regaining of their speech," added Chen, Associate Professor of Otolaryngology - Head and Neck Surgery at Harvard Medical School.

Hearing loss affects more than 1.5 billion people worldwide, with congenital deafness making up about 26 million of those individuals. For hearing loss in children, more than 60 per cent have a genetic cause.

DFNB9 for example, is a hereditary disease caused by mutations of the OTOF gene and a failure to produce a functioning otoferlin protein, which is necessary for the transmission of the sound signals from the ear to the brain.

There are currently no FDA-approved drugs to help with hereditary deafness, which has opened the door for new solutions like gene therapies.

In the trial, the six children with DFNB9 were observed over a 26-week period at the Eye & ENT Hospital of Fudan University in China.

The team collaborators utilised an adeno-associated virus (AAV) carrying a version of the human OTOF gene to carefully introduce the gene into the inner ears of the patients through a special surgical procedure. Differing doses of the single injection of the viral vector were used.

All six children in the study had total deafness, as indicated by an average auditory brainstem response (ABR) threshold of more than 95 decibels.

After 26 weeks, five children demonstrated hearing recovery, showing a 40-57 decibel reduction in ABR testing, dramatic improvements in speech perception and the restored ability to conduct normal conversation.

Overall, no dose-limiting toxicity was observed. While following up on the patients, 48 adverse events were observed, with a significant majority (96 per cent) being low grade, and the rest being transitory with no long-term impact.

The study provides evidence of the safety and effectiveness of gene therapies in treating DFNB9, as well as their potential for other forms of genetic hearing loss. Moreover, the results contribute to an understanding of the safety of AAV insertion into the human inner ear, the team said.