By Yishane Lee
The cornerstone of Hearing Health Foundation, ever since its founding in 1958 as the Deafness Research Foundation, has been funding early-career researchers who bring innovative thinking to hearing and balance research. HHF’s Emerging Research Grants (ERG) are awarded to the most promising scientists in the field, with many going on to earn prestigious National Institutes of Health backing.
HHF is always proud to see ERG grantees thrive in their careers and research. Most recently, two ERG scientists funded in the mid-1990s have made headlines, each for treatments for noise-induced hearing loss (NIHL).
1996 and 1997 ERG scientist John Oghalai, M.D., of the University of Southern California, coauthored a study showing promise for preventing NIHL. Published May 7, 2018, in the Proceedings of the National Academy of Sciences, Oghalai and team used miniature optics to examine the mouse cochlea after exposure to extremely loud noise, and found that in addition to immediate hair cell death, a fluid buildup in the inner ear over several hours eventually led to nerve cell loss. The fluid buildup, or endolymph hydrops, contributes to synaptopathy, or damage to the auditory nerve cell synapse. In a USC News press release, Oghalai described the excess fluid as a feeling of fullness and ringing in the ear that a person may experience after attending a loud concert.
Because the extra fluid showed a high concentration of potassium, the team saw a method to re-balance the fluids that naturally occur in the inner ear by injecting a salt (sodium) and sugar solution into the middle ear three hours after exposure. Nerve cell loss was reduced by 45 to 64 percent, which may help preserve hearing. The researchers see applications for this treatment for military service members who experience blast trauma as well as for people who have Ménière’s disease, the hearing and balance condition that is associated with inner ear fluid buildup.
Images from the cochleae of guinea pigs show the presence of more hair cells in animals treated with a short interfering RNA that interrupts a gene upregulated after damage (right; control on left). Inner and outer hair cells (IHC and OHC) are labeled in green, stereocilia in yellow, and nuclei in blue. Arrowheads indicate ectopic hair cells. Credit: The Scientist via Molecular Therapy.
1996 ERG scientist Richard Kopke, M.D., FACS, of the Hough Ear Institute in Oklahoma, spent more than 20 years serving with the U.S. Army, becoming well aware of the dangers of NIHL for service members. In a paper in Molecular Therapy, published online in March 2018, Kopke and colleagues used “small interfering RNAs” (siRNAs) to block the activity of the Notch signaling pathway gene Hes1 that itself blocks hair cell differentiation in developing supporting cells and may contribute to the failure of hair cells to regenerate after injury.
These siRNAs were delivered using nanoparticles directly injected to the cochleae of live, adult guinea pigs. Kopke’s team had previously shown using siRNAs to block Hes1 to be effective in regenerating hair cells in cultured mouse cochlea. In the current study, the 24-hour, sustained-release of siRNAs through nanoparticles three days after deafening resulted in the recovery of some hearing ability, measured using auditory brainstem responses, at three weeks and continuing to nine weeks, when the study ended. Compared with the control mice, the RNA-injected mice showed less overall hair cell loss and early signs of immature hair cell development, which the authors say may signal hair cell regeneration. Hearing loss caused by noise, chemotherapy drugs, or aging that damages or kills hair cells are all targets for this potential treatment.
In an article in The Scientist, HHF’s Hearing Restoration Project consortium member Jennifer Stone, Ph.D., who was not involved in the paper, echoed the study authors in saying further research should work to determine which cells are turning into hair cells, and whether the observed hair cell development is truly new hair cells and not the repair of damaged hair cells. Kopke and team plan to test the treatment using longer periods between deafening and injection, while also modifying dose and delivery.
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