title: Translational issues in cochlear synaptopathy.
abstract: Understanding the biology of the previously underappreciated sensitivity of cochlear synapses to noise insult, and its clinical consequences, is becoming a mission for a growing number of auditory researchers. In addition, several research groups have become interested in developing therapeutic approaches that can reverse synaptopathy and restore hearing function. One of the major challenges to realizing the potential of synaptopathy rodent models is that current clinical audiometric approaches cannot yet reveal the presence of this subtle cochlear pathology in humans. This has catalyzed efforts, both from basic and clinical perspectives, to investigate novel means for diagnosing synaptopathy and to determine the main functional consequences for auditory perception and hearing abilities. Such means, and a strong concordance between findings in pre-clinical animal models and clinical studies in humans, are important for developing and realizing therapeutics. This paper frames the key outstanding translational questions that need to be addressed to realize this ambitious goal.
authors.affiliation: Decibel Therapeutics, 215 First St, Cambridge, MA, 02142, USA. Electronic address: ahickox@decibeltx.com.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Hickox
authors.affiliation: Decibel Therapeutics, 215 First St, Cambridge, MA, 02142, USA. Electronic address: elarsen@decibeltx.com.
authors.forename: Erik
authors.initials: E
authors.lastname: Larsen
authors.affiliation: Speech, Language, and Hearing Sciences and Biomedical Engineering, Purdue University, 715 Clinic Drive, West Lafayette, IN, 47907, USA. Electronic address: mheinz@purdue.edu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Heinz
authors.affiliation: Decibel Therapeutics, 215 First St, Cambridge, MA, 02142, USA. Electronic address: lshinobu@decibeltx.com.
authors.forename: Leslie
authors.initials: L
authors.lastname: Shinobu
authors.affiliation: Decibel Therapeutics, 215 First St, Cambridge, MA, 02142, USA. Electronic address: jwhitton@decibeltx.com.
authors.forename: Jonathon P
authors.initials: JP
authors.lastname: Whitton
mesh_terms: D000818:Animals; D003051:Cochlea / Q000473:pathology* / Q000503:physiopathology; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D006317:Hearing Loss, Noise-Induced / Q000453:epidemiology / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D009622:Noise / Q000009:adverse effects*; D011237:Predictive Value of Tests; D015995:Prevalence; D013045:Species Specificity; D013569:Synapses / Q000473:pathology*; D009435:Synaptic Transmission; D057170:Translational Research, Biomedical / Q000379:methods*
keywords: Cochlear synaptopathy; Hidden hearing loss; Noise-induced hearing loss