Zheng-Yi Chen, DPhil, on Looking Deeper Into Effects of Gene Therapy on OTOF Deafness


The associate professor of otolaryngology from Harvard Medical School discussed further research being pursued with AAV1-hOTOF gene therapy.

“The one major limitation of cochlear implants is music appreciation, which is completely different than what we experience. So, we're doing a study to see whether they have a better sense of music appreciation, they can hear the pitch, frequency and everything embedded in the music, because we know how important that is to a person.”

Five out of 6 children with autosomal recessive deafness 9 (DFNB9) caused by mutations of the OTOF gene experienced significant, clinically meaningful improvements in hearing after receiving AAV1-hOTOF gene therapy. The participants were treated as part of a clinical trial conducted in collaboration with investigators from Mass Eye and Ear at the Eye & ENT Hospital of Fudan University in Shanghai, China.

The participants had hearing recovery, improvements in speech recovery, and significant reductions in the average auditory brainstem response. In the 1 nonresponding participant, the investigators theorized that the nonresponse may have been due to their higher concentration of neutralizing antibodies at baseline, or, alternatively, a possible leakage of the AAV1-hOTOF solution from the round window membrane during or after surgery. There were no serious adverse events or dose-limiting toxicities.

CGTLive spoke with study investigator Zheng-Yi Chen, DPhil, associate scientist, Eaton-Peabody Laboratories, Mass Eye and Ear, and associate professor, Otolaryngology–Head and Neck Surgery, Harvard Medical School, to learn more about the progress of the trial. He also shared some other research efforts ongoing with AAV1-hOTOF gene therapy, including effects on music appreciation.

Lu J, Wang H, Cheng X, et al. AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial. Lancet. Published online January 24, 2024. doi: 10.1016/S0140-6736(23)02874-X
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