Author: Stump, Elizabeth
Date published: January 1, 2010
Journal code: DRFH
A drug to cure hearing loss? It is not yet available in your local drugstore, but scientists are optimistic about what the future holds.
More than 36 million Americans have hearing impairment due to aging, disease, ototoxic drugs, noise and genetics, and the number is increasing each year, according to the Hearing Loss Association of America. And the increase is not all due to aging baby boomers - anyone can suffer permanent hearing damage from excessive and repeated exposure to loud noise.
Upwards of 30 million people in the United States regularly face dangerous levels of noise at work, in such industries as construction, mining, agriculture, aviation, manufacturing and transportation. In fact, hearing loss is among the most common forms of disability among military veterans, according to the 2005 Institute of Medicine's report, "Noise and Military Service: Implications for Hearing Loss and Tinnitus."
Small wonder then that, during this past decade, there has been mounting interest in the development of drugs to prevent and treat hearing loss and, in particular, noise-induced hearing loss (NIHL).
For more than 15 years, Richard D. Kopke, M.D., CEO of the Hough Ear Institute in Oklahoma City, Okla., has studied NIHL with the aim of developing a preventive treatment.
"Despite decades of hearing conservation, which has been needed and helpful, NIHL is still one of the most common causes of deafness," says Kopke. Drug treatments are necessary because hearing protection can be "uncomfortable, inconvenient, impair hearing acuity and can oftentimes be only partially effective," Kopke says. Even the most sophisticated earplugs cannot dampen noise received through the skull. "The skull easily transmits very loud, damaging noise directly to the cochlea where damage occurs, bypassing earplugs," Kopke explains.
Loud noise causes the release of toxins, called free radicals, in the cochlea (the inner ear organ of hearing), which in turn causes damage to the delicate hair cells and nerve endings in the cochlea and leads to the death of irreplaceable sensory cells needed for hearing.
The loss of these cells proceeds in a predictable pattern called "apoptosis," says Donald H. Henderson, Ph.D., professor of communicable disorders and sciences at the Center for Hearing and Deafness at the University at Buffalo, in Buffalo, N.Y., who has studied NIHL for years.
Before studies showing that NIHL is largely caused by the production of free radicals, NIHL was thought to be caused primarily by intense vibrations, produced by loud noises, that tear the structures of the inner ear. Then with the discovery of the role of free radicals came the possibility that a pharmaceutical could be formulated to neutralize them.
Kopke and Henderson collaborated on the exploration of two classes of drugs to prevent - and, to a limited degree, treat - free radical damage, thereby preventing NIHL.
"The first class of drugs is antioxidants, which are related to the body's normal antioxidant protection system," Henderson says. Antioxidants are nutrients found naturally in the body, in fruits and vegetables and in vitamins A, C and E, and they basically eliminate free radicals, according to Henderson.
The researchers discovered that repeated exposure to nontoxic noise increased the levels of antioxidants in the inner ear. "The logic is that if free radicals are normally neutralized by antioxidants, and if noise greatly increases free radical formation, augmenting the ear's antioxidant supply helps prevent serious damage."
SRC-inhibitors are the second class of drug Kopke and Henderson explored. These drugs block the cell death process (apoptosis). While these drugs have worked well in laboratory studies with mice, rats and chinchillas, there is limited data on their efficacy with humans in noisy environments, says Henderson.
Studies from Henderson's lab show that the SRC protein tyrosine kinase (PTK) may be involved in initiating both metabolic and mechanically induced apoptosis in sensory cells of the cochlea. In research published in Hearing Research in 2005, chinchillas were given SRC inhibitors on the round window membrane of their inner ears and a type of placebo was placed on the other ear. The chinchillas were then exposed to noise. Twenty days later, analysis of their cochleae showed that all three of the SRC inhibitors under trial (KX1-004, KX1-005 and KX1-174) provided protection from noise at 106 decibels. Additional tests, varying the noise exposure, were conducted with the most effective drug, KX1-004. For all conditions, results suggested an active role for SRC-PTK in NIHL. Henderson's research on SRC-PTK inhibitors to prevent NIHL is ongoing.
NAC Shows Promise
In 2004, Henderson and Kopke performed a significant human clinical study on the safety, tolerability and effectiveness of Nacetylcystine, or NAC, a relatively safe antioxidant compound, as a hearing protection drug for Marines in battle. (NAC was approved by the FDA over 25 years ago for treating liver damage from overuse of acetaminophen.) NAC had been studied for more than eight years in the laboratory and tested successfully in mice and chinchillas for hearing loss, but this was the first study on humans.
In the pilot study, approximately 650 military personnel - all of whom used earplugs - were given either low oral doses of dissolvable NAC during training or a placebo. NAC was found to be safe and well tolerated, with the same side effects as the placebo, and it appeared to reduce the incidence of hearing loss by 25 percent compared to the placebo, reports Kopke. These preliminary results are currently under peer review.
"Because of the initial encouraging results, two more clinical studies were initiated in the military. The first study is a repeat of the previous study with weapons noise using a higher dose of NAC. The second study looks at using NAC to reduce NIHL on an aircraft carrier," Kopke says.
NAC has several beneficial effects, says Kopke. "It neutralizes the toxins, it helps the injured tissue to repair itself and it prevents some of the injured cells from dying. The result is a substantial lessening of permanent deafness than the noise would have normally caused. It is most effective if given before noise exposure and then continued during noise exposure but it can also be somewhat effective if given shortly after loud noise exposure."
The NAC antioxidant compound is currently available as a dietary supplement under the name The Hearing Pill by American BioHealth Group in San Diego, Calif., which used the patent from Kopke's studies and acquired the license to develop the drug into an easily usable form.
According to the Web site (www.thehearingpill. com), the pill is "indicated for helping the remediation of the mechanisms that lead to permanent hearing loss, either before or shortly after noise trauma, after diagnosis by a qualified physician." The site urges those taking the pill to also use external hearing protection.
But this isn't a patent for a miracle cure, experts caution. NAC is still not FDA-approved as a treatment for NIHL. Rigorous scrutiny and further testing in humans is warranted before it is safe to expect that the supplements or any pill on the market can prevent NIHL. The FDA determined that NAC in a small dose is a nutraceutical - a name for foods claimed to have a medicinal effect on human health - rather than a pharmaceutical, and did not need regulatory approval to be sold. Unlike drugs, nutritional supplements aren't subject to FDA regulation. Compared with the dosage of SRC-inhibitors, a higher dosage of NAC is required, says Henderson.
In Kopke's Oklahoma City lab, research continues on the development of drug approaches for the prevention and treatment of NIHL. "Although initial results with NAC are encouraging, the damage and cell death mechanisms involved in noise-induced deafness are very complex," he said. "Therefore we have been performing additional studies with a combination of NAC and other safe antioxidants including a nitrone. We have found that the combination treatment is considerably more effective, allows the dose of medicine to be lowered, and increases the time window for giving the medicine after noise exposure from four to 24 hours."
It may only be a matter of time before protective drugs for people exposed to dangerous noise levels become a possible solution, echoes Henderson. These drugs could take the form of a pill or nutritional bar and act as a supplement to boost the defenses of anyone, but especially industrial workers, soldiers and musicians.
For now, head to your local drugstore - for earplugs. Minding the risk factors for hearing loss and taking preventative measures like wearing ear protection and limiting noise exposure is still your best defense.
Elizabeth Stump is a medical writer and assistant editor at Springer Publishing in New York City. She is also the editor-in-chief of the Hearing Loss Association of America, Manhattan Chapter monthly newsletter. In addition to writing, Elizabeth enjoys reading, sports and fitness and exploring New York City.