Preclinical Testing of Tetrandrine against Noise-Induce Hearing Loss

DESCRIPTION provided by applicant Noise is the most common occupational and environmental hazard thus it is not surprising that noise induced hearing loss NIHL is the second most common form of sensorineural hearing deficit second only to age related hearing loss Although therapeutics that target the free radical pathway have shown promise for reducing NIHL there are no medications approved by the U S Food and Drug Administration for NIHL Development of an efficacious treatment has been hampered by the complex array of cellular and molecular pathways involved in NIHL Therefore a new approach is necessary to combat these multiple signaling pathways in order for therapeutics to be successful at preventing and treating NIHL Recent preclinical studies have demonstrated that calcium channel blockers and anti inflammatory drugs can prevent NIHL Tetrandrine TET a bis benzylisoquinoline alkaloid originally purified from a Chinese medicinal herb shows strong promise as a NIHL therapeutic due to its antioxidant and anti inflammatory properties as well as its ability to block calcium channels Moreover the use of TET clinically has shown a long term safety profile Based on our preliminary findings that TET could protect against NIHL in this Phase I STTR application we will determine the median effective dose ED for this drug to prevent Aim and treat Aim NIHL in two different animal models The innovative aspects in our approach for using TET are TET already has well characterized pharmacological properties and a long history of clinical applications and TET is known to intervene in multiple signaling pathways involved in NIHL We will use the data from these studies to complete an Investigational New Drug IND enabling data package for our SBIR phase II clinical studies of this agent The goal of this program is to bring TET to market for use in prevention and treatment of NIHL PUBLIC HEALTH RELEVANCE The work in this proposal is very relevant to the development of pharmacologic interventions for noise induced permanent hearing loss More than million people in the USA are exposed to hazardous levels of noise on a regular basis This proposal will discover new drugs to prevent and treat NIHL and if successful provide sufficient preclinica data for future clinical trials to prevent permanent hearing loss