A new study co-led by investigators from Mass Eye and Ear, a member of Mass General Brigham, demonstrated the effectiveness of a gene therapy in restoring hearing function for children suffering from hereditary deafness.
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In a trial of six children taking place at the Eye and ENT Hospital of Fudan University in Shanghai, China, the researchers found the novel 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.
With its first patient treated in December 2022, this research represents the first human clinical trial to administer gene therapy for treating this condition, with the most patients treated and the longest follow-up to date.
Their results were published January 24 in The Lancet.
"If children are unable to hear, their brains can develop abnormally without intervention," said Zheng-Yi Chen, DPhil, an associate scientist in the Eaton-Peabody Laboratories at Mass Eye and Ear and associate professor of Otolaryngology–Head and Neck Surgery at Harvard Medical School.
"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."
In order to test this novel treatment, six children with DFNB9 were observed over a 26-week period at the Eye and ENT Hospital of Fudan University.
The Mass Eye and Ear collaborators utilized 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%) being low grade, and the rest being transitory with no long-term impact. ■