Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila

Namita Agrawal, Judit Pallos, Natalia Slepko, Barbara L. Apostol, Laszlo Bodai, Ling Wen Chang, Ann Shyn Chiang, Leslie Michels Thompson, J. Lawrence Marsh

Research output: Contribution to journalArticle

125 Citations (Scopus)


We explore the hypothesis that pathology of Huntington's disease involves multiple cellular mechanisms whose contributions to disease are incrementally additive or synergistic. We provide evidence that the photoreceptor neuron degeneration seen in flies expressing mutant human huntingtin correlates with widespread degenerative events in the Drosophila CNS. We use a Drosophila Huntington's disease model to establish dose regimens and protocols to assess the effectiveness of drug combinations used at low threshold concentrations. These proof of principle studies identify at least two potential combinatorial treatment options and illustrate a rapid and cost-effective paradigm for testing and optimizing combinatorial drug therapies while reducing side effects for patients with neurodegenerative disease. The potential for using prescreening in Drosophila to inform combinatorial therapies that are most likely to be effective for testing in mammals is discussed.

Original languageEnglish
Pages (from-to)3777-3781
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
Publication statusPublished - Mar 8 2005



  • Combinatorial treatments
  • Neurodegeneration

ASJC Scopus subject areas

  • General

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