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

Gene Therapy volume 6, pages 1648–1660 (1999)Cite this article

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.

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Acknowledgements

Special consideration is extended to Joel Ito and Vince Warren for their artistic and photographic support. Copyright release was received and gratefully acknowledged from Cell Transplantation and Cognizant Communication Corporation to allow re-publication of text and selected Figures and Tables from a previous publication (Rohrer DC, Nilaver G, Nipper V, Machida CA, Genetically modified PC12 brain grafts: survivability and inducible nerve growth factor expression. Cell Transplantation 1996; 5: 57–68). TCW is now a medical student at Loma Linda University School of Medicine in Loma Linda, California. DCR is now a practicing physician and neurosurgeon with Microneurosurgical Consultants, PC (9155 SW Barnes Road, Suite 440, Portland, Oregon 97225). CAM is supported by NIH RR00163, HL42358, and DK53462, and is an American Heart Association Established Investigator.

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Authors and Affiliations

  1. Division of Neuroscience, Oregon Regional Primate Research Center, Oregon Health Sciences University, Beaverton, OR, USA

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

  2. Division of Neurosurgery Neuroscience, Oregon Health Sciences University, Portland, OR, USA

    D C Rohrer

  3. Department of Neurology Neuroscience, Oregon Health Sciences University, Portland, OR, USA

    G Nilaver

  4. Department of Cell and Developmental Biology Neuroscience, Oregon Health Sciences University, Portland, OR, USA

    G Nilaver

  5. Department of Biochemistry and Molecular Biology Neuroscience, Oregon Health Sciences University, Portland, OR, USA

    C A Machida

  6. Graduate Program in Neuroscience, Oregon Health Sciences University, Portland, OR, USA

    C A Machida

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Wyman, T., Rohrer, D., Kirigiti, P. et al. Promoter-activated expression of nerve growth factor for treatment of neurodegenerative diseases. Gene Ther 6, 1648–1660 (1999). https://doi.org/10.1038/sj.gt.3300989

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