By looking for a way to regenerate hair cells – sensory cells that allow hearing – researchers have shed light on a possible new gene therapy for hearing loss and deafness.
- There are 6 million deaf people in France. Few solutions for deafness exist because damaged or destroyed hair cells cannot regenerate.
- Researchers have discovered a drug cocktail of different molecules that succeeded in regenerating mouse hair cells by reprogramming a series of genetic pathways in the inner ear.
- However, research is still needed before setting up a clinical trial on humans.
According to’Pastor Institute, France has 6 million deaf people. There are few solutions for deafness. Indeed, when the hair cells are damaged or destroyed, they cannot regenerate. The work of the center Mass Eye and Ear which belongs to the American hospital network Mass General Brigham, open the way to a possible new treatment.
Hair cells: the elements allowing regeneration identified
In previous work, researcher Zheng-Yi Chen studied zebrafish and chickens – whose hearing cells can regenerate unlike those of humans. He then highlighted two pathways responsible for inducing the cell division necessary to create new hair cells: the Notch and Myc cell signaling pathways. While these results were interesting, they presented a major problem: the “humans cannot activate the Myc and Notch pathways like a switch”explains the press release published on April 18, 2023.
The scientist and his team then sought to find out if a treatment could enable them to be activated. Through single cell sequencing, they found that activation of Myc and Notch signaling pathways resulted in stimulation of two other pathways: Wnt and cAMP. “Most importantly, they found chemical compounds that can directly activate Wnt and cAMP. They then used small biological molecules, called small interfering RNAs (siRNAs), to knock out genes that suppressed Myc pathway activation”explains the press release.
“Think of a brake when driving a car”explained the lead author “if the brake is still engaged, you can’t drive. We found an siRNA that could remove the brake from this genetic pathway”.
Deafness: a cocktail of chemicals, molecules and gene therapy
In their latest essays presented on April 17, 2023 in the journal Proceedings of the National Academy of Sciences, scientists combined chemical compounds with siRNA molecules. To boost efficacy, the Atoh1 gene was also placed through a gene therapy approach using a harmless adenovirus. This “mixture” was introduced into the inner ear of an adult mouse whose hair cells were damaged.
The researchers then discovered that “this drug-like cocktail combined with an adenovirus, activated Myc and Notch. This resulted in the regeneration of new hair cells”. These hearing cells were confirmed to be functional using advanced imaging and other techniques. However, further research is still needed before a clinical trial with people with hearing loss.
Lead author Zheng-Yi Chen is optimistic: “If we can combine surgery with a method of delivering gene therapy, we hope we can achieve our number one goal: to bring a new treatment to the medical world.”
