Promoter-activated expression of nerve growth factor for treatment of neurodegenerative diseases.
Genetic transfer approaches have received recent consideration as potential treatment modalities for human central and peripheral nervous system (CNS and PNS, respectively) neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Transplantation of genetically modified cells into the brain represents a promising strategy for the delivery and expression of specific neurotrophic factors, neurotransmitter-synthesizing enzymes, and cellular regulatory proteins for intervention in neurodegenerative diseases. The use of specific regulatable promoters may also provide potential control of gene expression required for dose-specific or time-specific therapeutic strategies. In this article, we review the potential use of activated promoters in ex vivo systems for the potential genetic therapy of neurodegenerative disorders, and then describe our own studies using the zinc-inducible metallothionein promoter for the regulated expression of nerve growth factor (NGF) in rodent brain transplants.
Wyman
T
T
Division of Neuroscience, Oregon Regional Primate Research Center, Oregon Health Sciences University, Beaverton, OR 97006, USA.
Rohrer
D
D
Kirigiti
P
P
Nichols
H
H
Pilcher
K
K
Nilaver
G
G
Machida
C
C
D000818:Animals; D001921:Brain / Q000378:metabolism; D016380:Brain Tissue Transplantation; D002272:Carcinoembryonic Antigen / Q000235:genetics; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000235:genetics; D016332:Fetal Tissue Transplantation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007763:Lac Operon; D008222:Lymphokines / Q000235:genetics; D008668:Metallothionein / Q000235:genetics; D020932:Nerve Growth Factor / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000628:therapy*; D011401:Promoter Regions, Genetic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D002272:Carcinoembryonic Antigen; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D008668:Metallothionein; D020932:Nerve Growth Factor