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Gene Therapy Restores Hearing in Mice

Study findings set the stage for human trials
Animation of an illustration of mouse


esearchers from the Miller School and Harvard Medical School report successfully using gene therapy to help restore hearing in a mouse model mimicking genetic hearing loss in humans. The next step is to study the therapy in humans with a common type of genetic hearing loss.

“Hearing loss affects 15% to 26% of the world’s population,” said Xue Zhong Liu, M.D., Ph.D., the Marian and Walter Hotchkiss Endowed Chair in Otolaryngology at the Miller School and one of the corresponding authors of the study, which was published in Molecular Therapy. “The gene TMPRSS3 is necessary for normal hearing, and mutations in TMPRSS3 account for about 9% of genetic hearing loss. TMPRSS3 mutations affect function and survival of inner ear and hearing nerve cells, which have been associated with age-related hearing loss.”

Hearing loss associated with mutations in TMPRSS3 can range from mild to profound and is generally progressive. “Patients with these mutations have significant amounts of residual hearing. This would make it an attractive target for potential rescue therapy,” Dr. Liu said.

The Miller School researchers recommended focusing the study on the most common form of TMPRSS3 mutations, called DFNB8, which has been reported across populations. The researchers also generated the mouse model used in this study, which mimicked postlingual hearing loss in TMPRSS3 patients.

“In humans with this mutation, hearing loss does not manifest until adulthood. Much like humans, mice with the mutation develop delayed hearing loss, which made the model valuable for the study,” Dr. Liu said.

The investigators found that a single injection of gene therapy targeted to the mutation resulted in sustained recovery of auditory function in the mouse model. They are continuing their collaboration and have started to conduct an international multicenter study on this form of hearing loss to prepare for human gene therapy trials.

FALL 2023