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Brain Advance Access published online on January 28, 2004
Brain, doi:10.1093/brain/awh103
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© 2004 The Guarantors of Brain

Article

Protective effect of herpes simplex virus-mediated neurotrophin gene transfer in cisplatin neuropathy

Munmun Chattopadhyay 1, James Goss 2, Darren Wolfe 3, William C. Goins 3, Shaohua Huang 3, Joseph C. Glorioso 3, Marina Mata 2, and David J. Fink 4*

1 Departments of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA
2 Departments of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA; GRECC, VA Pittsburgh Healthcare System, Pittsburgh, PA 15213, USA
3 Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15213, USA
4 Departments of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15213, USA; 1914 Taubman Center, 1500 E Medical Center Drive, Ann Arbor, MI 48109, USA

* Corresponding author. E-mail: djfink{at}umich.edu.

Received 20 July 2003 ; revised 11 December 2003 ; accepted 14 December 2003

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.

Keywords: nerve growth factors; gene therapy; herpes; neuropathy
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