Noninvasive System to Deliver Therapeutic Hypothermia for Protection Against Noise-Induced Hearing Loss

Project Summary Noise-induced hearing loss (NIHL) is global public health risk and is an impairment resulting from irreversible damage caused to the sensitive structures and neural elements in the cochlea. A Center for Disease Control and Prevention report highlights that 24% of adults and 17% of teenagers in the United States experience hearing loss in one or both ears from exposure to occupational or recreational loud sound. NIHL has a high prevalence among members of the armed forces and is a serious public health concern associated with loss of productivity, and high health care costs. Globally, occupational noise exposure is responsible for 16% of disabling hearing loss (over 600 million people); with significant lifetime costs per person in the US alone. While several pharmacological agents have shown promising results in preclinical trials and/or entered early clinical trials, at present there is no clinically available strategy to reduce or prevent NIHL. Preliminary and prior published results show that controlled and localized therapeutic hypothermia provided to the inner ear post-NIHL or post- mechanical trauma conserves significant residual hearing and preserves sensitive neural structures. The benefits of therapeutic hypothermia have long been discussed for improved neurological outcomes following traumatic brain injuries and cardiac arrest. This Phase I SBIR proposal will be used to design, build and test systems and protocols to deliver mild therapeutic hypothermia non-invasively to the inner ear during the critical time window following noise trauma. Using computational models of heat transfer and studies from cadaveric temporal bones, this study aims to translate such devices to clinical practice. Successful completion of these Phase I studies will enable Restor-Ear Devices LLC to submit a q-sub for an investigational device exemption (IDE) to the Food and Drug Administration and a future Phase II SBIR application to test efficacy and safety of therapeutic hypothermia against NIHL in human subjects. Considering that the prevalence of hearing loss is expected to increase significantly in the next few decades, these studies will be a first step toward establishing therapeutic hypothermia as a technique for preservation of hearing. It is likely that our systems will find further applications for protecting auditory and vestibular functions against ototoxic insults, traumatic brain injuries, blast exposures, and inner ear or middle ear surgeries.Public health relevance: The proposed work in this phase I SBIR application by Restor-Ear Devices LLC is aimed at designing and building prototype systems to deliver therapeutically safe, controllable and localized mild hypothermia to the human ears for conserving residual hearing and neural structures following noise overexposure. We will utilize numerical stimulations and cadaver temporal bone studies to derive optimal design(s) of therapeutic hypothermia system. Successful completion of proposed studies will lead to an innovative neuroprotective and treatment paradigm to conserve long-term hearing function and improve human health.