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BRIEF COMMUNICATION Neuroprotective Effects of Encapsulated CNTF-Producing Cells in a Rodent Model of Huntington’s Disease Are Dependent on the Proximity of the Implant to the Lesioned Striatum

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Abstract:

Huntington’s disease (HD) is a devastating genetic disorder with no effective treatments for preventing or lessening the underlying neuronal degeneration. Intracerebral delivery of CNTF in animal models of HD has shown considerable promise as a means of protecting striatal neurons that would otherwise be destined to die. The present study examines whether the neuroprotective effects of CNTF require that the delivery be immediately proximal to the lesion site or whether protective effects can be exerted when the delivery site is more distal to the site of injury. Encapsulated CNTF-producing cells were implanted into the lateral ventricle either ipsilateral or contralateral to an intrastriatal quinolinic acid (QA) injection. A robust neuroprotective effect was observed only in those animals receiving CNTF implants ipsilateral to the QA injection. In these animals, the loss of striatal ChAT and GAD activity as well as the behavioral impairments that resulted from QA were completely prevented. In contrast, no neurochemical or behavioral benefits were produced by implants of CNTF-producing cells in the contralateral ventricle. These data continue to support the use of cellular delivery of CNTF for HD but caution that delivery directly to the striatum may be needed if any clinical benefits are to be seen.

Keywords: CNTF; Fibroblasts; Gene therapy; Huntington’s disease; Neurotrophic factors; Polymer encapsulation; Quinolinic acid

Document Type: Short Communication

DOI: http://dx.doi.org/10.3727/000000004783983981

Affiliations: 1: *LCT BioPharma, Cranston, RI 02921 2: †Department of Surgery, Oregon Health and Science University, Portland, OR 97239

Publication date: January 1, 2004

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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