Gene Therapy Using Adeno Virus Reverses Age-Related Hearing Loss

The efficacy of adeno-associated virus (AAV) vectors in aged animal models with genetic changes equivalent to a defective TMPRSS3 human gene, which typically results in progressive hearing loss has been demonstrated by a team of researchers from Mass Eye and Ear, a member of Mass General Brigham. As reported in Molecular Therapy, researchers observed robust hearing rescue in the aged mice upon injecting the animals with an AAV carrying a healthy human TMPRSS3 gene. This is the first to successfully demonstrate the use of viral vectors in gene therapy for hearing loss.

Hearing loss (HL) is one of the most common sensory deficit disorders that affect about 466 million people. By 2050, one in 10 individuals is expected to live with some form of hearing loss. Of the hundreds of millions of cases of hearing loss affecting individuals worldwide, genetic hearing loss is often the most difficult to treat (1^✔ ✔Trusted Source
Hereditary hearing loss: From human mutation to mechanism

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Genetic HL affects 1 in 500 newborns. There are no treatments available to reverse or prevent genetic deafness. While hearing aids and cochlear implants offer limited relief, no available treatment can reverse or prevent this group of genetic conditions, prompting scientists to evaluate gene therapies for alternative solutions.

Gene Therapy Rescues Hearing for the First Time in Aged Mouse Models

As the inner ear is an isolated organ that can be accessed safely by local injection, many gene replacement and overexpression studies targeting HL have been conducted successfully, resulting in hearing rescue (2^✔ ✔Trusted Source
Neonatal AAV gene therapy rescues hearing in a mouse model of SYNE4 deafness

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Rapid progress has been made in the understanding of the genetic etiology of human HL. Genetic testing and diagnosis of HL provide essential information for further genetic therapies. TMPRSS3 protein is necessary for normal hearing in mammals. TMPRSS3 gene mutations account for approximately 12%–13% of HL families that are negative for common genetic mutations.

Adeno-associated virus (AAV), a non-replicative viral vector with low immunogenicity and little ototoxicity, is one of the most promising gene therapy tools. 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 (3^✔ ✔Trusted Source
Rescue of auditory function by a single administration of AAV-TMPRSS3 gene therapy in aged mice of human recessive deafness DFNB8

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Since humans are born with fully developed ears, this proof-of-concept is necessary before testing the intervention in humans with genetic hearing loss.

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The new study 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 genetic hearing loss even at an advanced age. The study also establishes the feasibility of other gene therapies in the aged population.

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References:

1. Hereditary hearing loss: From human mutation to mechanism - (https://www.sciencedirect.com/science/article/abs/pii/S0378595511001602)
2. Neonatal AAV gene therapy rescues hearing in a mouse model of SYNE4 deafness - (https://www.embopress.org/doi/full/10.15252/emmm.202013259)
3. Rescue of auditory function by a single administration of AAV-TMPRSS3 gene therapy in aged mice of human recessive deafness DFNB8 - (https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(23)00261-7?)

Source-Eurekalert