Novel gene therapy could help reverse age-related hearing loss one day

The researchers successfully demonstrated the efficacy of adeno-associated virus (AAV) therapy.
Mrigakshi Dixit
Representational image
Representational image


Hearing loss has been identified as one of the most rapidly growing health issues. By 2050, one out of every ten people will most likely have some form of hearing loss. Among all types of hearing loss problems, the one caused by genetics is often regarded as incredibly difficult to treat. Cochlear implants (electronic devices to improve hearing) can be used in some cases, but they provide only limited relief. Therefore, gene therapies are the only potential treatment options. 

To address this issue, a team of researchers successfully demonstrated the efficacy of adeno-associated virus (AAV) therapy. This is the first time that researchers from Mass Eye and Ear, a treatment and research center affiliated with Harvard Medical School, have demonstrated the use of AAV in aged animal models. 

AAV is not a new therapy; in fact, it has been tested in neonatal animals. “Despite having already rescued hearing in neonatal animals with genetic defects, the vectors have yet to demonstrate this ability in fully mature or aged animal models,” reveals the official statement

Testing AAV efficacy

In this new study, the team went on test the efficacy of AAV in aged animal models. They tweaked an aged mouse model with a hearing loss mutation similar to a "defective" TMPRSS3 gene, which causes this problem in humans. As per the study, individuals with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10, which leads to progressive hearing loss.  

Using AAV as a vector, the team administered the gene therapy containing a healthy TMPRSS3 into the aged animals. The findings demonstrated that a single dose of this therapy resulted in significant improvements in the animals' hearing. 

“Our findings suggest that a virally mediated gene therapy, either by itself or in combination with a cochlear implant, could potentially treat genetic hearing loss. This was also the first study that has rescued hearing in aging mice, which points to the feasibility of treating DFNB8 patients with DFNB8 even at an advanced age. The study also establishes the feasibility of other gene therapies in the aged population,” said Zheng Yi Chen, D.Phil., an investigator in the Eaton-Peabody Laboratories at Mass Eye and Ear, in the official release. 

This new study paves the way for the development of clinical treatments for the elderly population, which could eventually reverse hearing loss to some extent.

The results have been published in the journal Molecular Therapy.

Study abstract:

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. A single AAV2-hTMPRSS3 injection in Tmprss3A306T/A306T mice of an average age of 18.5 months leads to sustained rescue of the auditory function to a level similar to wild-type mice. AAV2-hTMPRSS3 delivery rescues the hair cells and the spiral ganglions neurons. This study demonstrates successful gene therapy in an aged mouse model of human genetic deafness. It lays the foundation to develop AAV2-hTMPRSS3 gene therapy to treat DFNB8 patients, as a standalone therapy or in combination with cochlear implantation.

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