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

T. C. Wyman, D. C. Rohrer, P. Kirigiti, H. V. Nichols, K. Y. Pilcher, G. Nilaver, C. A. Machida

Research output: Contribution to journalReview article

31 Scopus citations

Abstract

Genetic transfer approaches have received recent consideration as potential treatment modalities for human central and peripheral nervous system (CNS and PNS, respectively) neurodegenrative disorders, including Parkinsons' 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.

Original languageEnglish (US)
Pages (from-to)1648-1660
Number of pages13
JournalGene therapy
Volume6
Issue number10
DOIs
StatePublished - Oct 1 1999

Keywords

  • Brain transplant
  • Gene transfer
  • Nerve growth factor
  • Promoter-activated vectors
  • Regulatable promoters

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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