In tests on fruit flies, Larry Marsh and Leslie Thompson found that combinatorial drug therapies developed from these compounds halted the brain-cell damage caused by the fatal, progressive neurodegenerative disorder. Such types of therapies have proven very effective in the treatment of other complex human diseases, like cancers and AIDS. And while any human benefits from this study are years off, the research provides the first evidence that a regimen of complementary drugs can treat Huntington's. Study results appear this week in the early online edition of the Proceedings of the National Academy of Sciences.
"Preclinical testing strategies such as those we used with fruit flies can result in a great savings of cost and time in developing potential disease treatments," Marsh said. "They can serve to rapidly identify treatment regimens that are very likely to provide effective therapeutic benefit to patients."
In developing these drug combinations, Marsh and Thompson chose compounds that individually have been shown in other fruit-fly tests and in mouse models to suppress neurodegeneration, but each targets different cellular processes. Included in these combinations are HDAC inhibitors, which also are showing great promise in cancer-treatment clinical trials. When combined, these compounds showed increased suppression qualities with no toxic side effects.
"That's what's important to note," Marsh said. "Every drug is also a potential poison. Thus, we sought to find several drugs, each of which impacts a different point in the disease process, so that we could use low doses of each single drug, but together their combined effects all converge on a single disease process. This minimizes toxic side effects while maximizing benefit."