Viral vectors for neurotrophic factor delivery: a gene therapy approach for neurodegenerative diseases of the CNS.
The clinical manifestation of most diseases of the central nervous system results from neuronal dysfunction or loss. Diseases such as stroke, epilepsy and neurodegeneration (e.g. Alzheimer's disease and Parkinson's disease) share common cellular and molecular mechanisms (e.g. oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction) that contribute to the loss of neuronal function. Neurotrophic factors (NTFs) are secreted proteins that regulate multiple aspects of neuronal development including neuronal maintenance, survival, axonal growth and synaptic plasticity. These properties of NTFs make them likely candidates for preventing neurodegeneration and promoting neuroregeneration. One approach to delivering NTFs to diseased cells is through viral vector-mediated gene delivery. Viral vectors are now routinely used as tools for studying gene function as well as developing gene-based therapies for a variety of diseases. Currently, many clinical trials using viral vectors in the nervous system are underway or completed, and seven of these trials involve NTFs for neurodegeneration. In this review, we discuss viral vector-mediated gene transfer of NTFs to treat neurodegenerative diseases of the central nervous system.
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, United States.
Seung T
ST
Lim
Mikko
M
Airavaara
Brandon K
BK
Harvey
D000818:Animals; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D009416:Nerve Regeneration; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D057170:Translational Research, Biomedical; D016896:Treatment Outcome
D009414:Nerve Growth Factors