A commentary on glial cell line-derived neurotrophic factor (GDNF). From a glial secreted molecule to gene therapy.
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.
Bohn
M C
MC
Children's Memorial Institute for Education and Research, Northwestern University Medical School, Chicago, IL 60614, USA. m-bohn@nwu.edu
D000818:Animals; D004298:Dopamine / Q000502:physiology; D015316:Genetic Therapy; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D016472:Motor Neuron Disease / Q000188:drug therapy; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy
C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D004298:Dopamine