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Viral vector strategy for glial cell line-derived neurotrophic factor therapy for stroke.

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta superfamily. Over the last decade, GDNF has been shown to promote regenerative and restorative effects on dopaminergic neurons. Accumulating evidence also demonstrates that administration of GDNF to areas of ischemic brain injury limits cerebral infarction and reduces damage to motor functions in animal models of stroke. Neurotrophic factor and anti-apoptotic mechanisms, among others, have been proposed to underlie the therapeutic effects of GDNF. A major obstacle for GDNF therapy is the protein delivery to the brain, as well as its sustained bioavailability over time. Gene therapy and the use of viral vectors offer a technique for longevity of GDNF expression within the brain. In this review, we consider the risks and benefits of GDNF gene therapy as it relates to the treatment of stroke.