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In vivo gene therapy for pyridoxine‐induced neuropathy by herpes simplex virus‐mediated gene transfer of neurotrophin‐3
Author(s) -
Chattopadhyay Munmun,
Wolfe Darren,
Huang Shaohua,
Goss James,
Glorioso Joseph C.,
Mata Marina,
Fink David J.
Publication year - 2002
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10061
Subject(s) - neurotrophin , herpes simplex virus , dorsal root ganglion , neurotrophic factors , sensory system , neurotrophin 3 , peripheral nervous system , peripheral neuropathy , in vivo , genetic enhancement , sensory neuron , neuroscience , medicine , biology , immunology , virus , central nervous system , receptor , gene , endocrinology , brain derived neurotrophic factor , genetics , diabetes mellitus
Neurotrophic factors have been demonstrated to prevent the development of peripheral neuropathy in animal models, but the therapeutic use of these factors in human disease has been limited by the short serum half‐life and dose‐limiting side effects of these potent peptides. We used peripheral subcutaneous inoculation with a replication‐incompetent, genomic herpes simplex virus‐based vector containing the coding sequence for neurotrophin‐3 to transduce sensory neurons of the rat dorsal root ganglion in vivo, and found that expression of neurotrophin‐3 from the vector protected peripheral sensory axons from neuropathy induced by intoxication with pyridoxine assessed by electrophysiological (foot sensory response amplitude, and conduction velocity, and H‐wave), histological (nerve morphology and morphometry), and behavioral measures of proprioceptive function. In vivo gene transfer using herpes simplex virus vectors provides a unique option for treatment of diseases of the sensory peripheral nervous system.