Dopaminergic neurons protected from degeneration by GDNF gene therapy.
Glial cell line-derived neurotrophic factor (GDNF) supports growth and survival of dopaminergic (DA) neurons. A replication-defective adenoviral (Ad) vector encoding human GDNF injected near the rat substantia nigra was found to protect DA neurons from the progressive degeneration induced by the neurotoxin 6-hydroxydopamine (6-OHDA) injected into the striatum. Ad GDNF gene therapy reduced loss of DA neurons approximately threefold 6 weeks after 6-OHDA lesion, as compared with no treatment or injection of Ad lacZ or Ad mGDNF (encoding a biologically inactive deletion mutant GDNF). These results suggest that Ad vector-mediated GDNF gene therapy may slow the DA neuronal cell loss in humans with Parkinson's disease.
Choi-Lundberg
D L
DL
Department of Neurobiology and Anatomy, University of Rochester, Box 603, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Lin
Q
Q
Chang
Y N
YN
Chiang
Y L
YL
Hay
C M
CM
Mohajeri
H
H
Davidson
B L
BL
Bohn
M C
MC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000502:physiology*; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009410:Nerve Degeneration; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents; D016627:Oxidopamine; D016716:PC12 Cells; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D019076:Transgenes
C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D016627:Oxidopamine; D004298:Dopamine