A team of researchers at the University of Pittsburgh School of Medicine have identified the molecular mechanisms behind resilience to noise-induced tinnitus in an animal model which has brought to light a possible drug therapy that may reduce people’s susceptibility to tinnitus.
“Tinnitus is typically induced by exposure to loud noise and causes whistling, clicking, roaring and other phantom sounds. It is estimated that 5 to 15 percent of Americans suffer from tinnitus, said Thanos Tzounopoulos, Ph.D., associate professor and member of the auditory research group in the Department of Otolaryngology, Pitt School of Medicine, where he also holds the auditory physiology endowed chair.”
The research is based on previous studies of mouse models, which have shown that hyperactive dorsal cochlear nucleus (DCN) cells seem to be linked to tinnitus. These DCN cells fire impulse even when no noise is present causing the phantom sound to be perceived. The cause of this hyperactivity was found to be due to a reduction in tiny channels, called KCNQ channels, which channel potassium ions in and out of the cell.
This research has brought to light KCNQ channel activators as a clinical candidate for the prevention of tinnitus development.
“However, a significant percentage of people are exposed to loud sounds and never develop tinnitus, and there was little known about why that is. That’s what we set out to examine in this study,” Dr. Tzounopoulos said.”
The most recent study looked at mice that had been exposed to loud noise and did not develop tinnitus. The study found a reduction in KCNQ2/3 channel activity, after which a recovery of KCNQ2/3 activity and a reduction in hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity was seen.
The HCN channel is another stream through which positively charged ions move between cells. Researchers hope that by combining drugs that enhance KCNQ2/3 channel activity and reduce HCN channel activity they may have a treatment that increases the tinnitus sufferer’s resilience and reduces their susceptibility to the condition.
“We have already developed novel activators of KCNQ2/3 channels. The next step, in collaboration with Dr. Peter Wipf, a medicinal chemist from the University of Pittsburgh, is to develop specific blockers of HCN channels,” Dr. Tzounopoulos said.”