In vivo gene therapy for pyridoxine-induced neuropathy by herpes simplex virus-mediated gene transfer of neurotrophin-3

Ann Neurol. 2002 Jan;51(1):19-27. doi: 10.1002/ana.10061.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal
  • Cells, Cultured
  • Disease Models, Animal
  • Electrophysiology
  • Ganglia, Spinal / cytology
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Vectors*
  • Motor Activity
  • Neurons, Afferent / cytology
  • Neurons, Afferent / physiology
  • Neurotrophin 3 / genetics*
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / pathology
  • Peripheral Nervous System Diseases / therapy*
  • Pyridoxine*
  • Rats
  • Sciatic Nerve / pathology
  • Simplexvirus / genetics*


  • Neurotrophin 3
  • Pyridoxine