New therapy has potential to repair cells damaged by noise, prevent hearing loss

More than 700 million people worldwide suffer from some degree of hearing loss, including an estimated 20 percent of Americans over the age of 12, according to medical experts.

In fact, the World Health Organization predicts that more than 1 billion teenagers and young adults are at risk of noise-induced hearing loss (NIHL) by using personal listening devices at hazardous volume levels.

Treating and preventing NIHL is complicated, however, because overexposure to noise triggers three separate types of damage to the cochlea-;the part of the inner ear involved in hearing.

Loud noise promotes the proliferation of reactive oxygen species (ROS), a type of free radical that injures the molecules of the cochlea; it stimulates inflammation in the cochlea; and it damages the DNA of the cochlea.

Audiologist and molecular biologist O'neil Guthrie, an associate professor in NAU's Department of Communication Sciences and Disorders, is collaborating with New Jersey-based Optigenex on a three-year contract totaling $551,000.

Guthrie will conduct a pre-clinical investigation of a novel therapy using the company's patented ac-11 technology based on carboxy alkyl esters, which help the body's natural ability to repair DNA.

Guthrie believes this therapy, which will be administered as a single oral formulation, has the potential to repair cells damaged by noise and prevent hearing loss. As an added benefit, the technology can also target ROS and inflammation to prevent cell death in the cochlea.

By developing a single drug given orally as a vitamin or gummy that addresses all three problems, Guthrie hopes to make the drug as safe and effective as possible, avoiding unknown or poorly understood interactions between multiple drugs and their side effects.

The drug could be taken by a construction worker, for example, before using a jackhammer, or by a concert-goer after attending a loud concert. Members of the U.S. military stand to benefit from this technology as well, notes Guthrie, since hearing loss and hearing-related dysfunctions are the most frequent service-related war injuries-;even more frequent than traumatic brain injury and post-traumatic stress disorder.

Even after more than 100 years of research on hearing loss, there is still no widely accepted biomedical treatment or prevention. Our current work has the potential to resolve this issue. If we're successful, this solution will be able to prevent hearing loss even after exposure to a traumatic level of noise."

O'neil Guthrie

Guthrie approached Optigenex as a potential collaborator on the project and has been pleased with the results.

"Optigenex has supported research on DNA repair and I conduct research on DNA repair, so I approached them to collaborate," he said. "My experience with Optigenex has been excellent. They are science-oriented and driven to produce the best product possible."

"We are delighted to be supporting Dr. Guthrie and his staff at NAU on such an important application of our patented technology," said Optigenex President and CEO Dan Zwiren. "Dr. Guthrie's preliminary data coupled with our work in DNA repair suggests we may have a solution to address the burgeoning medical issue of hearing loss due to the exposure to high decibel noise."

As director of NAU's Cellular and Molecular Pathology Lab, Guthrie will work with his lab group to conduct this research. He plans to hire two research specialists in 2020. The project also will provide opportunities for both graduate and undergraduate students to participate in research.

"The possibility of finally developing a treatment for hearing loss is particularly exciting," Guthrie said. "This is because, in addition to being a research scientist, I am also a licensed clinical audiologist with more than 17 years' experience, so I am familiar with the day-to-day struggles of individuals who suffer with hearing loss."

If the clinical studies succeed as planned, the next step would be conducting clinical trials to more precisely define dosing and timing.

Since 2008, Guthrie has been studying the mechanisms that lead to hearing loss in order to identify targeted treatment strategies. His basic science research program is focused on revealing molecular mechanisms that regulate the integrity of active genes and the engineering of biomedical approaches to enhance the capacity of cells to protect their DNA.

To this end, Guthrie's research group employs a range of genetic, epigenetic, molecular and pharmacologic strategies to regulate cellular DNA repair capacity.

The research from this work has led to patented and unpatented molecular constructs that could affect clinical outcomes. In addition to his basic science research program, Guthrie is also interested in translational research that improves clinical and epidemiology outcomes.

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