Browsing by Subject "Hearing Loss, Noise-Induced"

Now showing 1 - 3 of 3

Open Access
Integrating pharmacogenomics into clinical trials of hearing disorders.
(The Journal of the Acoustical Society of America, 2022-11) Brutnell, Thomas P; Wang, Xinwen; Bao, Jianxin
In 2019, the U.S. Food and Drug Administration issued guidance to increase the efficiency of drug development and support precision medicine, including tailoring treatments to those patients who will benefit based on genetic variation even in the absence of a documented mechanism of action. Although multiple advancements have been made in the field of pharmacogenetics (PGx) for other disease conditions, there are no approved PGx guidelines in the treatment of hearing disorders. In studies of noise-induced hearing loss (NIHL), some progress has been made in the last several years associating genomic loci with susceptibility to noise damage. However, the power of such studies is limited as the underlying physiological responses may vary considerably among the patient populations. Here, we have summarized previous animal studies to argue that NIHL subtyping is a promising strategy to increase the granularity of audiological assessments. By coupling this enhanced phenotyping capability with genetic association studies, we suggest that drug efficacy will be better predicted, increasing the likelihood of success in clinical trials when populations are stratified based on genetic variation or designed with multidrug combinations to reach a broader segment of individuals suffering or at risk from NIHL.
Open Access
Noise-induced hearing disorders: Clinical and investigational tools.
(The Journal of the Acoustical Society of America, 2023-01) Le Prell, Colleen G; Clavier, Odile H; Bao, Jianxin
A series of articles discussing advanced diagnostics that can be used to assess noise injury and associated noise-induced hearing disorders (NIHD) was developed under the umbrella of the United States Department of Defense Hearing Center of Excellence Pharmaceutical Interventions for Hearing Loss working group. The overarching goals of the current series were to provide insight into (1) well-established and more recently developed metrics that are sensitive for detection of cochlear pathology or diagnosis of NIHD, and (2) the tools that are available for characterizing individual noise hazard as personal exposure will vary based on distance to the sound source and placement of hearing protection devices. In addition to discussing the utility of advanced diagnostics in patient care settings, the current articles discuss the selection of outcomes and end points that can be considered for use in clinical trials investigating hearing loss prevention and hearing rehabilitation.
Open Access
Otoprotective Effects of Stephania tetrandra S. Moore Herb Isolate against Acoustic Trauma.
(Journal of the Association for Research in Otolaryngology : JARO, 2018-12) Yu, Yan; Hu, Bing; Bao, Jianxin; Mulvany, Jessica; Bielefeld, Eric; Harrison, Ryan T; Neton, Sarah A; Thirumala, Partha; Chen, Yingying; Lei, Debin; Qiu, Ziyu; Zheng, Qingyin; Ren, Jihao; Perez-Flores, Maria Cristina; Yamoah, Ebenezer N; Salehi, Pezhman
Noise is the most common occupational and environmental hazard, and noise-induced hearing loss (NIHL) is the second most common form of sensorineural hearing deficit. Although therapeutics that target the free-radical pathway have shown promise, none of these compounds is currently approved against NIHL by the United States Food and Drug Administration. The present study has demonstrated that tetrandrine (TET), a traditional Chinese medicinal alkaloid and the main chemical isolate of the Stephania tetrandra S. Moore herb, significantly attenuated NIHL in CBA/CaJ mice. TET is known to exert antihypertensive and antiarrhythmic effects through the blocking of calcium channels. Whole-cell patch-clamp recording from adult spiral ganglion neurons showed that TET blocked the transient Ca²⁺ current in a dose-dependent manner and the half-blocking concentration was 0.6 + 0.1 μM. Consistent with previous findings that modulations of calcium-based signaling pathways have both prophylactic and therapeutic effects against neural trauma, NIHL was significantly diminished by TET administration. Importantly, TET has a long-lasting protective effect after noise exposure (48 weeks) in comparison to 2 weeks after noise exposure. The otoprotective effects of TET were achieved mainly by preventing outer hair cell damage and synapse loss between inner hair cells and spiral ganglion neurons. Thus, our data indicate that TET has great potential in the prevention and treatment of NIHL.