PROJECT SUMMARY
The most common occupational and environmental hazard in this country is noise. It's
not surprising, then, that noise-induced hearing loss (NIHL) is the second most common
form of sensorineural hearing deficit, behind only age-related hearing loss
(presbycusis). Although therapeutics that target the free radical pathway have shown
promise for reducing NIHL, there are no effective nutraceuticals or approved
medications for NIHL. Development of an efficacious treatment has been hampered by
the complex array of cellular and molecular pathways involved in NIHL. Our preliminary
studies have shown that the Chinese herb Stephania tetrandra and its main extract,
tetrandrine (TET), can effectively protect against NIHL in mice. Clinical use of this herb
has exhibited an excellent long-term safety profile. Moreover, TET possesses strong
antioxidant and anti-inflammatory properties, and can also block calcium channels, thus
targeting three main signaling pathways that underlie NIHL. Consistent with the funding
priorities at National Center for Complementary and Integrative Health, in this Phase I
application, we will determine the median effective dose (ED50) for this herb extract to
prevent (Aim 1) and treat (Aim 2) NIHL in rats using a long noise exposure model (8
hours per day) similar to most industrial working environments. The innovative aspects
of our approach are: (1) developing a nutraceutical against NIHL, thus breaking a major
access barrier for customers, who are more likely to visit audiologists for hearing
treatment; (2) testing in a rat model with cumulative noise exposure similar to that
encountered by factory workers; (3) selecting an herb with well-characterized
pharmacological properties and a long safety history of clinical applications; and (4)
targeting multiple signaling pathways that underlie NIHL. If the outcome of this study is
successful, we will then obtain institutional review board (IRB) approval to conduct SBIR
Phase II studies in humans of this nutraceutical against NIHL. The goal of our program
is to bring this nutraceutical to market for use in the prevention and treatment of NIHL. If
this approach is successful, similar nutraceuticals will be evaluated for potential
prevention of presbycusis.