Glial cell line-derived neurotrophic factor (
GDNF) was identified as a consequence of the hypothesis that glia secrete factors that influence growth and differentiation of specific classes of neurons. Glia are a likely source of additional
neurotrophic factors; however, this strategy has not been applied extensively. The discovery of
GDNF in 1993 led to an abundance of studies that within only a few years qualified
GDNF as a bona fide
neurotrophic factor. Of particular interest are studies demonstrating the effectiveness of
GDNF protein in ameliorating neurodegeneration in animal models of
Parkinson's disease and
amyotrophic lateral sclerosis (ALS). It remains to be determined whether
GDNF will be an effective
therapy in humans with these diseases. However, since these diseases are slowly progressive and the CNS relatively inaccessible, the delivery of
GDNF as a therapeutic molecule to the CNS in a chronic manner is problematic. Studies addressing this problem are applying viral vector mediated transfer of the
GDNF gene to the CNS in order to deliver biosynthesized
GDNF to a specific location in a chronic manner. Recent studies suggest that these
GDNF gene therapy approaches are effective in rat models of
Parkinson's disease. These studies are reviewed in the context of what developments will be needed in order to apply
GDNF gene therapy to the clinic.