Skip Navigation


Brain Advance Access originally published online on January 28, 2004
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
127/4/929    most recent
awh103v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (18)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Chattopadhyay, M.
Right arrow Articles by Fink, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chattopadhyay, M.
Right arrow Articles by Fink, D. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.