Protective effect of herpes simplex virus-mediated neurotrophin gene transfer in cisplatin neuropathy.
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.
Chattopadhyay
Munmun
M
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Goss
James
J
Wolfe
Darren
D
Goins
William C
WC
Huang
Shaohua
S
Glorioso
Joseph C
JC
Mata
Marina
M
Fink
David J
DJ
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
D000970:Antineoplastic Agents; D009414:Nerve Growth Factors; D009479:Neuropeptides; D002945:Cisplatin