Promoter-activated expression of nerve growth factor for treatment of neurodegenerative diseases

Gene Ther. 1999 Oct;6(10):1648-60. doi: 10.1038/sj.gt.3300989.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain Tissue Transplantation
  • Carcinoembryonic Antigen / genetics
  • Cell Line
  • Endothelial Growth Factors / genetics
  • Fetal Tissue Transplantation
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Humans
  • Lac Operon
  • Lymphokines / genetics
  • Metallothionein / genetics
  • Nerve Growth Factor / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / therapy*
  • Promoter Regions, Genetic*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Carcinoembryonic Antigen
  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Metallothionein
  • Nerve Growth Factor