Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adenoviridae / genetics
-
Animals
-
Corpus Striatum / metabolism
-
Corpus Striatum / pathology
-
Dopamine / physiology*
-
Gene Expression
-
Genetic Therapy*
-
Genetic Vectors
-
Glial Cell Line-Derived Neurotrophic Factor
-
Humans
-
Male
-
Molecular Sequence Data
-
Nerve Degeneration*
-
Nerve Growth Factors*
-
Nerve Tissue Proteins / genetics*
-
Neurons / pathology
-
Neurons / physiology
-
Neuroprotective Agents*
-
Oxidopamine
-
PC12 Cells
-
Parkinson Disease / pathology
-
Parkinson Disease / therapy*
-
Rats
-
Rats, Inbred F344
-
Substantia Nigra / metabolism
-
Substantia Nigra / pathology
-
Transgenes
Substances
-
GDNF protein, human
-
Gdnf protein, rat
-
Glial Cell Line-Derived Neurotrophic Factor
-
Nerve Growth Factors
-
Nerve Tissue Proteins
-
Neuroprotective Agents
-
Oxidopamine
-
Dopamine
Associated data
-
GENBANK/L19062
-
GENBANK/L19063