Gene Therapies Offer Hope for Treatment of Genetic Hearing Loss in Aged Population

Category Health

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A team of researchers from Mass Eye and Ear, part of Mass General Brigham, have successfully rescued hearing in aged mouse models of human recessive deafness DFNB8 using adeno-associated virus (AAV) vectors. This breakthrough suggests that the same techniques may be used to treat genetic hearing loss in humans aged population in the future.

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Researchers at Mass Eye and Ear, part of Mass General Brigham, have successfully used adeno-associated virus (AAV) vectors in gene therapies to treat genetic hearing loss in aged mouse models. This breakthrough suggests the potential for similar therapies to treat genetic hearing loss in the human aged population.

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. 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 therapies can also be used to treat other genetic conditions, such as retinal dystrophy, muscular dystrophy, and cystic fibrosis.

One of the most promising tools used in these therapies—adeno-associated virus (AAV) vectors—has galvanized the hearing-loss community in recent years. 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. Since humans are born with fully developed ears, this proof-of-concept is necessary before testing the intervention in humans with genetic hearing loss.

Adeno-associated virus (AAV) vectors are often used in gene therapy, as they have a low risk of triggering an immune response.

A team of researchers from Mass Eye and Ear, a member of Mass General Brigham, recently became the first to successfully demonstrate AAV vector efficacy in aged animal models when they developed a mature mouse model with a mutation equivalent to a defective TMPRSS3 human gene, which typically results in progressive hearing loss. 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.

The team of researchers from Mass Eye and Ear, a member of Mass General Brigham, used an AAV carrying a healthy human TMPRSS3 gene, equivalent to a defective gene typically resulting in progressive hearing loss.

"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," said corresponding author Zheng Yi Chen, D.Phil., an investigator in the Eaton-Peabody Laboratories at Mass Eye and Ear. "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." .

Approximately 900 million people have disabling hearing loss worldwide.

In the future, researchers hope to further explore and refine gene therapies for hearing loss and other genetic conditions, as well as evaluate the efficacy and safety of the treatments in clinical trials. This new advancement on the path to treating genetic hearing loss in the aged population is certainly momentous, but caution is still paramount as the potential risks of gene therapy must continuously be weighed against the likely benefits.

Dependant on the degree of hearing loss, treatment may involve the use of hearing aids, cochlear implants, or gene therapy.

Reference: "Rescue of auditory function by a single administration of AAV-TMPRSS3 gene therapy in aged mice of human recessive deafness DFNB8″ by Wan Du, Volkan Ergin, Corena Loeb, Mingqian Huang, Stewart Silver, Ariel Miura Armstrong, Zaohua Huang, Channabasavaiah B. Gurumurthy, Hinrich Staecker, Xuezhong Liu, and Zheng-Yi Chen, 26 May 2023, Molecular Therapy.DOI: 10.1016/j.ymthe.2023.05.005 .

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