Cystamine and intrabody co-treatment confers additional benefits in a fly model of Huntington's disease

S. F. Bortvedt, J. A. McLear, A. Messer, A. J. Ahern-Rindell, W. J. Wolfgang

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Huntington's disease (HD) is a lethal, neurodegenerative disorder caused by expansion of the polyglutamine repeat in the Huntingtin gene (HTT), leading to mutant protein misfolding, aggregation, and neuronal death. Feeding a Drosophila HD model cystamine, or expressing a transgene encoding the anti-htt intracellular antibody (intrabody) C4-scFv in the nervous system, demonstrated therapeutic potential, but suppression of pathology was incomplete. We hypothesized that a combinatorial approach entailing drug and intrabody administration could enhance rescue of HD pathology in flies and that timing of treatment would affect outcomes. Feeding cystamine to adult HD flies expressing the intrabody resulted in a significant, additional rescue of photoreceptor neurodegeneration, but no additional benefit in longevity. Feeding cystamine during both larval and adult stages produced the converse result: longevity was significantly improved, but increased photoreceptor survival was not. We conclude that cystamine-intrabody combination therapies can be effective, reducing neurodegeneration and prolonging survival, depending on administration protocols.

Original languageEnglish (US)
Pages (from-to)130-134
Number of pages5
JournalNeurobiology of Disease
Volume40
Issue number1
DOIs
StatePublished - Oct 2010
Externally publishedYes

Keywords

  • Combinatorial therapy
  • Neurodegenerative disease
  • Polyglutamine
  • ScFv

ASJC Scopus subject areas

  • Neurology

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