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Targeted Induction of Endogenous Neural Stem and Progenitor Cells-Chapter 5:A New Strategy for Gene Therapy of Neurological Disease

Elsevier Inc.
DOI: 10.1016/b978-012397632-1/50006-x
  • Medicine


Publisher Summary The chapter discusses the use of viral expression vectors to mobilize resident neural stem and progenitor cells as an effective strategy for treating a wide variety of neurological diseases, particularly the geographically and phenotypically restricted neurodegenerative diseases. In these disorders, the reconstruction of precise neural circuits may depend upon the development of new neurons in situ, within the local context in which they reside, and from which they attract and extend site-specific afferents and efferents. The mobilization of endogenous progenitor cells by gene therapeutic vectors, and the directed differentiation of their daughter cells into discrete neuronal and glial phenotypes in situ, proves as a strategy for eliciting CNS repair. Neural stem and progenitor cells are distributed in several discrete niches in the adult vertebrate brain. These cells may respond to injury or disease with a limited degree of compensatory neurogenesis, but the clinical importance of this response seems at best limited. The resident progenitor cells can be induced to generate substantial numbers of new neurons by stimulation with both delivered and virally expressed growth factors. Such directed induction is efficacious in the subcortical and striatal neurodegenerations such as Huntington's disease.

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