Gene therapy trial restores hearing in both ears to deaf children | Science

Five children who were born deaf have had hearing restored in both ears after taking part in an “amazing” gene therapy trial that raises hopes for future treatments.

The children could not hear due to inherited genetic mutations that alter the body’s ability to produce a protein needed to ensure that hearing signals pass smoothly from the ear to the brain.

Doctors at Shanghai’s Fudan University treated the children, ages one to 11, in both ears in the hope that they would regain enough three-dimensional hearing to participate in conversations and determine which direction sounds were coming from.

Within a few weeks of receiving the therapy, the children had regained their hearing, could locate the sources of sounds, and recognized speech in noisy environments. Two of the children were recorded dancing to music, the researchers reported in Nature Medicine.

Dr. Zheng-Yi Chen, a scientist at Massachusetts Eye and Ear, a Harvard teaching hospital in Boston who co-led the trial, said the results were “astonishing,” adding that researchers continued to see that children’s hearing ability “was progressing dramatically.”

The therapy uses an inactivated virus to smuggle functional copies of the affected gene, Otof, into the inner ear. Once inside, ear cells use the new genetic material as a template to produce functional copies of the crucial protein, otoferlin.

Video images of the patients show a two-year-old boy responding to his name three weeks after treatment and dancing to music after 13 weeks, having shown no response to either before receiving the injections.

A screenshot of footage showing one of the trial participants during hearing tests at Fudan University in Shanghai. Photo: Fudan University Eye and Ear, Nose and Throat Hospital/The Lancet

Another patient, a three-year-old girl, does not react to sounds, but 13 weeks after treatment she can understand sentences and pronounce some words.

The oldest patient, an 11-year-old girl, did not respond to tones played at different pitches before therapy, but she responded to all of them six weeks later and was able to participate in speech training starting at 13 weeks.

More than 430 million people worldwide are affected by disabling hearing loss, of whom around 26 million are deaf from birth.

Up to 60% of childhood deafness is due to genetic factors. The children in the trial suffer from a disease called DFNB9, caused by Otof mutations, which accounts for 2-8% of all congenital hearing loss.

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In January, the same Chinese-American team reported improvements after treating children who were deaf in one ear, but the intention was always to restore hearing to both ears. If they can hear with both ears, children can determine where sounds are coming from, an important skill for everyday situations like talking in groups and watching for traffic when crossing the street, the researchers said.

Larger trials will be needed to evaluate the benefits and risks of the therapy in more detail. The gene therapy is injected during a minimally invasive surgical procedure, so treating both ears doubles the time patients spend in surgery. Treating both ears also increases the risk of a stronger immune reaction, which is triggered when the body’s defenses react to the virus delivering the therapy.

“Our hope is that this trial can be expanded and that this approach can also be tested for deafness caused by other genes or nongenetic causes,” Chen said. “Our ultimate goal is to help people regain their hearing regardless of the cause of their hearing loss.”

Last month, a British girl became the first person to have hearing restored in one ear after receiving similar gene therapy for hearing loss caused by Otof mutations.

Professor Manohar Bance, principal investigator of that trial, said the therapy marked a new era in the treatment of deafness.

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