Progressive hearing loss might be aided by gene-editing therapies that use tiny messengers to nudge cells to repair themselves, a study led by University of Florida Health has discovered.
The study was published in the journal Science Translational Medicine on Nov. 12.
A multidisciplinary team of researchers led by Mei He, Ph.D., an associate professor of pharmaceutics in the UF College of Pharmacy, and Xiaoshu Pan, Ph.D., a postdoctoral researcher in He’s lab, looked to extracellular vesicles — nano-sized, bubble-like packages that cells release to communicate with one another — in the search for new treatments for progressive, nonsyndromic hearing loss.
Hearing loss affects more than 450 million people worldwide, and up to 50% of cases have a genetic origin. While interventions like hearing aids and cochlear implants help offset the loss, they don’t address the underlying disease.
Genome editing techniques have gained popularity in recent years, using strands of RNA or adeno-associated virus molecules to deliver material that prompts a cell to change its DNA. But there are challenges: It can be toxic to patients, and there are limits to how much genetic material the technique can deliver.
These limitations led He’s team to build a new extracellular vesicle, or EV, platform used to develop gene therapy. With help from a $1.3 million award from the National Institutes of Health, the system will accelerate the progress of safe, high-capacity genome-editing products from the bench to the bedside, He said, with human clinical trials slated to begin in about three years.
“Unlike other small-scale systems built explicitly for the laboratory, our platform is naturally scalable and compatible with the Good Manufacturing Practice pipeline, which will make translation to human clinical trials and large-scale production much quicker and easier,” He said. “EVs have a large loading capacity that enables more effective treatment doses and are made of natural biomaterials, so there’s no risk of toxicity for humans. Because EVs are easily absorbed by the cell, they penetrate deeply into the tissue, resulting in better performance.”
In the study, He’s team collaborated with Hinrich Staecker, M.D., Ph.D., and Peixing Huang, Ph.D., from the University of Kansas Medical Center to inject EVs loaded with RNA material and protein complexes into the ear canal of hearing-impaired mice. As measured by auditory brainstem responses, the mice that received the EV treatment experienced hearing preservation.
“We observed functional recovery of hearing that was nearly comparable to age-matched, wild mice with normal hearing. This result demonstrates effective, in-vivo preservation of hearing loss through gene editing,” He said.
He’s team developed their EV platform so that it can pair with a variety of gene-editing materials to treat other genetic diseases. Because the platform can be customized, it would potentially be effective for any patient, regardless of their genetic mutations.
“Our technology can be applied to any disease for which gene therapy is useful, including breast cancer and muscle decline,” He said. “This is a highly exciting, breakthrough contribution to our field of research.”