Hope for age-related hearing loss with novel gene therapy

Age-related hearing loss impacts one in three adults between the ages of 64 and 75 in the US, and around half of these numbers are down to genes.

The extra kicker, though, is that because hearing involves a complex genetic toolkit, it also makes this kind of hearing loss incredibly difficult to treat.

A team of researchers has for the first time targeted age-related genetic hearing loss in a much older cohort of mice, which had a mutation of the human transmembrane serine protease 3 (TMPRSS3) gene that results in autosomal recessive deafness 8/10 (DFNB8/DFNB10).

Using an adeno-associated virus (AAV) as a vector, a popular delivery tool for gene therapy, the researchers from Massachusetts Eye and Ear administered a healthy TMPRSS3 gene, and a single dose showed a marked improvement in the animals’ hearing, which was sustained for five months before starting to dip.

It’s not the first time that research into gene therapy for genetic hearing loss has delivered promising results in mice models. When scientists administered hair-cell regulator protein EPS8 via an AAV, they found it was able to restore genetic hearing loss. Another study saw the focus shift to the gene STRC, again delivered via AAV, and again showing positive results.

This latest study is the only one so far to successfully show the reversal of hearing loss in older animals.

“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,” said corresponding author Zheng Yi Chen, an investigator in the Eaton-Peabody Laboratories at Mass Eye and Ear. “The study also establishes the feasibility of other gene therapies in the aged population.”

While this study focuses on the TMPRSS3 gene, the key to its effectiveness lies in the efficacy of the AAV vector. Until now, AAV gene therapy has only shown it could treat hearing loss in very young or neonatal animal models.

Like the earlier studies, a mouse model is far from human trials, however, this research progresses the use of AAV gene therapy for age-related hearing loss and opens the door to developing clinical treatment for an older population.

“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 Chen.

The study was published in the journal Molecular Therapy.

Source: Massachusetts Eye and Ear