Therapeutic gene transfer with herpes-based vectors: studies in Parkinson's disease and motor nerve regeneration.
We have examined the possibility of using herpes simplex virus (HSV)-based vectors to prevent neuronal cell death and enhance functional recovery after injury. In the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD) and after proximal spinal root injury, direct stereotactic injection of HSV-based vectors constructed to express the glial cell derived neurotrophic factor (GDNF) or the anti-apoptotic peptide Bcl-2 prevented neuronal death and enhanced recovery. Gene transfer may be useful in the treatment of neurologic disorders in which neuronal cell death occurs in a restricted anatomic distribution.
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
David J
DJ
Fink
Joseph
J
Glorioso
Marina
M
Mata
D000818:Animals; D001522:Behavior, Animal; D002452:Cell Count; D016923:Cell Death; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008161:Lumbosacral Region; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology* / Q000821:virology; D009409:Nerve Crush / Q000379:methods; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration / Q000235:genetics; D016627:Oxidopamine; D010300:Parkinson Disease / Q000628:therapy* / Q000662:veterinary / Q000821:virology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D018139:Simplexvirus / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism / Q000821:virology; D013266:Stilbamidines / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005456:Fluorescent Dyes; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D013266:Stilbamidines; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase