Combination Therapy for Noise-Induced Hearing Loss

February 2011

Combination therapy-the use of two or more drugs in combination to treat an illness-is an effective way to treat such complex diseases as HIV/AIDS and cancer. Now some researchers are wondering if it might be effective in treating noise induced hearing loss (NIHL) too. The causes of NIHL involve a number of complex cellular and molecular pathways. Some of these pathways are already targeted by FDA-approved drugs for the treatment of other diseases. Researchers from the Washington University in St. Louis wondered,
1) if FDA-approved drugs that target these shared signaling pathways might be effective in preventing or treating NIHL, and
2) if so, is it possible to reduce their dosages-therefore to reduce their side effects-by combining two drugs that act on different signaling pathways?

Previous studies have shown that synthetic steroids, called corticoids, can prevent NIHL, and this team had recently found that anticonvulsants (for the treatment of epilepsy) can prevent permanent NIHL in mice. In this study, they investigated four drugs against NIHL, two drugs from the anticonvulsant family and two from the family of synthetic steroids. The researchers gave various doses of each drug to mice either two hours before exposing them to loud noise or 24 hours after exposure. After the range of effective dosages was determined for each drug, they applied a mathematical simulation to combine two drug families, and found that certain combinations were indeed effective in protecting against permanent hearing loss at lower dosages. They are currently applying for a patent on this discovery.

The researchers' next step is to examine the effects of the drug combination on animals that have a hearing range that is more similar to humans. They also plan to test the drug pairs on extremely loud noise, similar to what troops are facing on an Afghanistan battlefield.