title: Protective effect of herpes simplex virus-mediated neurotrophin gene transfer in cisplatin neuropathy.
abstract: Attempts to develop clinical treatments for neuropathy using neurotrophins have not been successful. We tested whether neurotrophin gene delivery to dorsal root ganglia (DRGs) using non-replicating herpes simplex virus (HSV)-based vectors could prevent the development of neuropathy caused by administration of cisplatin. Following subcutaneous inoculation of HSV vectors expressing nerve growth factor (NGF) or neurotrophin-3 (NT-3), neurons in the DRG were transduced to produce NGF or NT-3 in vivo. Inoculation of either the NGF- or the NT-3-expressing vectors 3 days before the start of a 6-week course of cisplatin treatment protected against cisplatin-induced neuropathy assessed by electrophysiological, histological and behavioural measures 2 months later. Iatrogenic neuropathy caused by administration of chemotherapeutic drugs represents an excellent target for a human trial to assess the potential of gene therapy to prevent neuropathy.
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Munmun
authors.initials: M
authors.lastname: Chattopadhyay
authors.forename: James
authors.initials: J
authors.lastname: Goss
authors.forename: Darren
authors.initials: D
authors.lastname: Wolfe
authors.forename: William C
authors.initials: WC
authors.lastname: Goins
authors.forename: Shaohua
authors.initials: S
authors.lastname: Huang
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Glorioso
authors.forename: Marina
authors.initials: M
authors.lastname: Mata
authors.forename: David J
authors.initials: DJ
authors.lastname: Fink
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D009431:Neural Conduction; D009479:Neuropeptides / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D011434:Proprioception / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018139:Simplexvirus / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D009414:Nerve Growth Factors; D009479:Neuropeptides; D002945:Cisplatin