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Cystamine and ethyl-eicosapentaenoic acid treatment fail to prevent malonate-induced striatal toxicity in mice.

Abstract
Cystamine has demonstrated neuroprotective activity in a variety of studies, and is currently being evaluated in a human clinical trial in Huntington's disease (HD). Cystamine treatment of various genetic models of HD demonstrated protection against neurodegeneration and/or improvement in behavior. Given the need for a rapid screening tool for HD therapeutics, we assessed the potential therapeutic benefits of cystamine in a short-term acute toxicity murine model of striatal cell death. Cystamine did not provide neuroprotection against bilateral intrastriatal malonate injections in mice as measured by lesion size, loss of striatal volume, or decreased striatal neuronal counts. Similar results were obtained for treatment with another potential therapeutic agent that was protective in genetic mouse models of HD, the essential fatty acid ethyl-eicosapentaenoic acid. Our findings suggest that this toxic model is not reflective or predictive of findings in genetic mouse models, and may not be useful as a preclinical screen for HD therapeutics.
AuthorsSaskia N Sivananthan, Blair R Leavitt
JournalNeurobiology of aging (Neurobiol Aging) Vol. 32 Issue 12 Pg. 2326.e1-4 (Dec 2011) ISSN: 1558-1497 [Electronic] United States
PMID21741126 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Malonates
  • Neuroprotective Agents
  • eicosapentaenoic acid ethyl ester
  • malonic acid
  • Eicosapentaenoic Acid
  • Cystamine
Topics
  • Animals
  • Corpus Striatum (drug effects, pathology)
  • Cystamine (administration & dosage)
  • Disease Models, Animal
  • Eicosapentaenoic Acid (administration & dosage, analogs & derivatives)
  • Huntington Disease (chemically induced, pathology, prevention & control)
  • Injections, Intraventricular
  • Malonates (toxicity)
  • Mice
  • Neuroprotective Agents (administration & dosage)
  • Treatment Outcome

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