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Brain Advance Access originally published online on January 28, 2004
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Brain, Vol. 127, No. 4, 929-939, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh103

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

Munmun Chattopadhyay1, James Goss1,3, Darren Wolfe2, William C. Goins2, Shaohua Huang2, Joseph C. Glorioso2, Marina Mata1,3 and David J. Fink1,2,3

Departments of 1 Neurology and 2 Molecular Genetics and Biochemistry, University of Pittsburgh and 3 GRECC, VA Pittsburgh Healthcare System, Pittsburgh, PA 15213, USA

Correspondence to: Dr David Fink, 1914 Taubman Center, 1500 E Medical Center Drive, Ann Arbor, MI 48109.Email: djfink{at}umich.edu

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.

Key Words: nerve growth factors; gene therapy; herpes; neuropathy

Abbreviations: CGRP= calcitonin gene-related peptide; DRG = dorsal root ganglion; ELISA = enzyme-linked immunosorbent assay; HCMV IEp = human cytomegalovirus immediate-early promoter; HSV = herpes simplex virus; LAP2 = latency active promoter element; m.o.i. = multiplicity of infection; NGF = nerve growth factor; NT-3 = neurotrophin-3; SP = Substance P; trk = tyrosine receptor kinase

Received July 20, 2003. Accepted December 14, 2003.


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M. Chattopadhyay, C. Walter, M. Mata, and D. J. Fink
Neuroprotective effect of herpes simplex virus-mediated gene transfer of erythropoietin in hyperglycemic dorsal root ganglion neurons
Brain, April 1, 2009; 132(4): 879 - 888.
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