title: Towards Clinical Application of Neurotrophic Factors to the Auditory Nerve; Assessment of Safety and Efficacy by a Systematic Review of Neurotrophic Treatments in Humans.
abstract: Animal studies have evidenced protection of the auditory nerve by exogenous neurotrophic factors. In order to assess clinical applicability of neurotrophic treatment of the auditory nerve, the safety and efficacy of neurotrophic therapies in various human disorders were systematically reviewed. Outcomes of our literature search included disorder, neurotrophic factor, administration route, therapeutic outcome, and adverse event. From 2103 articles retrieved, 20 randomized controlled trials including 3974 patients were selected. Amyotrophic lateral sclerosis (53%) was the most frequently reported indication for neurotrophic therapy followed by diabetic polyneuropathy (28%). Ciliary neurotrophic factor (50%), nerve growth factor (24%) and insulin-like growth factor (21%) were most often used. Injection site reaction was a frequently occurring adverse event (61%) followed by asthenia (24%) and gastrointestinal disturbances (20%). Eighteen out of 20 trials deemed neurotrophic therapy to be safe, and six out of 17 studies concluded the neurotrophic therapy to be effective. Positive outcomes were generally small or contradicted by other studies. Most non-neurodegenerative diseases treated by targeted deliveries of neurotrophic factors were considered safe and effective. Hence, since local delivery to the cochlea is feasible, translation from animal studies to human trials in treating auditory nerve degeneration seems promising.
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands. aren.bezdjian@mail.mcgill.ca.
authors.forename: Aren
authors.initials: A
authors.lastname: Bezdjian
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands. V.J.C.Kraaijenga@umcutrecht.nl.
authors.forename: Véronique J C
authors.initials: VJ
authors.lastname: Kraaijenga
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands. D.Ramekers@umcutrecht.nl.
authors.forename: Dyan
authors.initials: D
authors.lastname: Ramekers
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands. H.Versnel@umcutrecht.nl.
authors.forename: Huib
authors.initials: H
authors.lastname: Versnel
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands. H.G.X.M.Thomeer@umcutrecht.nl.
authors.forename: Hans G X M
authors.initials: HG
authors.lastname: Thomeer
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands. S.Klis@umcutrecht.nl.
authors.forename: Sjaak F L
authors.initials: SF
authors.lastname: Klis
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands. W.Grolman@umcutrecht.nl.
authors.forename: Wilko
authors.initials: W
authors.lastname: Grolman
mesh_terms: D000818:Animals; D003056:Cochlear Nerve / Q000187:drug effects*; D006801:Humans; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic
chemical_list: D009414:Nerve Growth Factors
keywords: clinical trial; growth factor; inner ear; neurodegenerative disorders; neurotrophin; peripheral nervous system; translational medicine