New hair to heal hearing

Harvard genetic researchers have struck on a novel way to restore hearing loss from damage and old age … with gene therapy that regenerated hair cells in the inner ear:

A research team led by Zheng-Yi Chen, an HMS associate professor of otolaryngology and associate scientist in the Eaton-Peabody Laboratories at Mass Eye and Ear, reported creating a drug-like cocktail of different molecules that successfully regenerated hair cells in a mouse model by reprogramming a series of genetic pathways within the inner ear.

The researchers hope their novel findings, published April 17 in PNAS, could one day pave the way for clinical trials for a gene therapy that can be administered to people with hearing loss.

Through single-cell RNA sequencing, they discovered that activating Myc and Notch led to a downstream effect in which two other pathways, Wnt and cAMP, became activated. Importantly, they found chemical compounds that can directly activate Wnt and cAMP.

They then used small biological molecules called small interfering RNAs (siRNAs) to remove genes downstream that suppressed the activation of the Myc pathway.

“Think about a brake when driving a car,” explained Chen. “If the brake is always engaged, you can’t drive. We found an siRNA that could remove the brake in this genetic pathway.”

The researchers then combined the chemical compounds and siRNA molecules into a drug-like cocktail. They delivered it to the inner ear of a normal adult mouse with damaged hair cells — an important distinction, as wild-type, non-transgenic mice would be more translatable to humans.

You can read more of Chen’s research here, in PNAS.