Pitt Researchers Awarded $2 Million Grant to Develop Drug for Tinnitus

By: Anita Srikameswaran

Tinnitus researchers at the University of Pittsburgh School of Medicine and Dietrich School of Arts & Sciences were awarded a three-year, $2 million grant from the U.S. Department of Defense, Defense Medical Research and Development Program, to continue their effort to develop a new treatment for the condition.

More than 1.2 million veterans experience tinnitus, which is the perception of a ringing in the ears, and it is the most common service-connected disability. Currently, there is no cure, said principal investigator Dr. Thanos Tzounopoulos, UPMC Endowed Professor of Auditory Physiology and Vice Chair of Research, Department of Otolaryngology, Pitt School of Medicine.

In previous DoD-supported work, he and Dr. Peter Wipf, Distinguished University Professor of Chemistry at Pitt, redesigned an FDA-approved epilepsy drug called retigabine, which alters the transport of potassium ions through channels in the nerve cell membrane, to treat tinnitus, a disorder of hyper-excitation of nerve cells in auditory pathways.

They changed several structural components of retigabine to further increase its potency, as well as narrowed its targets to two potassium transport channels, KCNQ2/3, reducing the likelihood of drug side effects, such as urinary retention, skin discoloration and retinal changes of the eyes.

That new compound, known as RL-81, will now undergo further animal and lab testing with the aim of gathering needed preclinical data before human testing is initiated.

“We are very excited about RL-81’s potential to reduce the symptoms of tinnitus and ease the burden it puts on people who are affected by it,” Tzounopoulos said. “It was rationally designed, meaning we synthesized it to specifically address an underlying cause of tinnitus.”

In the second part of the newly funded project, the researchers will take a closer look at another kind of ion channel, called HCN. Their experiments showed mice that recovered normal hearing after prolonged or recurrent exposure to very loud noise had reduced activity in this channel.

“We want to see if there is a causal relationship between HCN channel activity and tinnitus resistance, and to try to develop an HCN-channel blocker,” Tzounopoulos said. “It might be that a combination of a drug that enhances KCNQ2/3 activity and one that reduces HCN activity could prevent tinnitus in otherwise susceptible people.”

*Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the DoD.