title: Drug discovery for hearing loss: Phenotypic screening of chemical compounds on primary cultures of the spiral ganglion.
abstract: In the United States there are, at present, no drugs that are specifically FDA approved to treat hearing loss. Although several clinical trials are ongoing, including one testing D-methionine that is supported by the US Army, none of these trials directly address the effect of noise exposure on cochlear spiral ganglion neurons. We recently published the first report of a systematic chemical compound screen using primary, mammalian spiral ganglion cultures in which we were able to detect a compound and others in its class that increased neurite elongation, a critical step in restoring cochlear synapses after noise induced hearing loss. Here we discuss the issues, both pro and con, that influenced the development of our approach. These considerations may be useful for future compound screens that target the same or other attributes of cochlear spiral ganglion neurons.
authors: Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Interdepartmental Neurosciences Program, Northwestern University, Chicago, IL, USA; Knowles Hearing Center, Northwestern University, Evanston, IL, USA. Electronic address: whitlon@northwestern.edu.
authors: Donna S
authors: DS
authors: Whitlon
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D006309:Hearing / Q000187:drug effects*; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008715:Methionine / Q000494:pharmacology*; D000071446:Neuronal Outgrowth / Q000187:drug effects; D009622:Noise / Q000009:adverse effects; D010641:Phenotype; D061251:Primary Cell Culture; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology; D046509:Tissue Culture Techniques
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008715:Methionine
keywords: Cochlea; Deafness; In vitro; Neurite; Phenotypic screening; Statins