Delivery of neurotrophic factors to neuronal targets: toward gene therapy in the CNS.
Neurotrophic factors are a large class of molecules that can influence neuronal survival, modulate neuronal function and induce axonal growth. They act on specific receptors in specific subsets of neurons and glia. Since their discovery, neurotrophic factors have received considerable interest as possible means for the treatment of neurodegenerative diseases and central nervous system (CNS) trauma. In vitro experiments, as well as studies in animal models of CNS disease, have supported the concept of neuroprotection as a new treatment strategy in degenerative neurologic disease, using neurotrophic factor delivery to CNS targets. Despite the encouraging results from animal studies, progress in adaptation of this treatment strategy to human disease has been slow and sometimes disappointing. One of the major keys for the successful use of neurotrophic factors in treating neurologic disease is the mode of delivery. Neurotrophic factors need to be specifically targeted and regionally restricted to the area of interest to achieve significant results without widespread, unwanted adverse effects. This article summarizes results from recent studies of neurotrophic factors in models of neurodegenerative diseases and CNS trauma and outlines current knowledge and future perspectives of trophic factor gene therapy in the CNS.
Blesch
A
A
Center for Neural Repair, Department of Neurosciences-0626, University of California-San Diego, La Jolla, California 92093-0626, USA.