Preclinical prospects of investigational agents for hearing loss treatment

ABSTRACT

Introduction

: Hearing loss has a high prevalence, with aging, noise exposure, ototoxic drug therapies, and genetic mutations being some of the leading causes of hearing loss. Health conditions such as cardiovascular disease and diabetes are associated with hearing loss, perhaps due to shared vascular pathology in the ear and in other tissues.

Areas Covered

: Issues in the design of preclinical research preclude the ability to make comparisons regarding the relative efficacy of different drugs of interest for possible hearing loss prevention or hearing restoration. This has not slowed the advancement of candidate therapeutics into human clinical testing. There is a robust pipeline with drugs that have different mechanisms of action providing diverse candidate therapies and opportunities for combination therapies to be considered.

Expert Opinion

: Much of the preclinical research literature lacks standard study design elements such as dose response testing, and lack of standardization of test protocols significantly limits conclusions regarding relative efficacy. Nonetheless, the many positive results to date have supported translation of preclinical efforts into clinical trials assessing potential human benefits. Approval of the first hearing loss prevention therapeutic is a major success, providing a pathway for other drugs to follow.

KEYWORDS:

• Hearing loss
• hearing loss prevention
• noise-induced hearing loss
• drug-induced hearing loss
• sensorineural hearing loss
• gene therapy

Article highlights

• Sensorineural hearing loss is a common age-related disability

• A second common cause of acquired hearing loss is noise exposure

• Medicines that prevent the development of hearing loss, or restore auditory function to those who have already lost hearing ability, are of high interest

• Many investigational agents show promise in pre-clinical animal models, but lack of standardization across experimental protocols limits comparisons across agents

• There is a growing body of data from human participants enrolled in clinical trials assessing diverse investigational medicines for the inner ear

• Approval of the first hearing loss prevention therapeutic is a major success, and there is reason to hope additional therapies will successfully navigate the regulatory approval process

Declaration of interest

C Le Prell has previously received contract funding and/or clinical trial material from industry partners including 3 M Inc., Sound Pharmaceuticals, Inc., Edison Pharmaceuticals, Inc., and Hearing Health Science, Inc. In the past five years, C Le Prell has served as a paid consultant/scientific advisor to Hearing Lab Technology/Lucid, AlphaSights, and Biogenerator STL. C Le Prell is an inventor on US Patents 8,927,528 and US 7,786,100 B2 owned by the University of Michigan.

The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed they have served as a consultant to Otonomy, Inc (company now dissolved), Spiral Therapeutics, CILcare and Audiocure. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

C Le Prell is currently supported by USAMRAA W81XWH-19-C-0054, JPC-8/SRMRP W81XWH1820014, the American Academy of Audiology Foundation, and the Emilie and Phil Schepps Professorship in Hearing Science.