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Researchers zero in on new drug combination strategy

CAMBRIDGE, Mass. (July 15, 2003) -- Modern drug discovery hinges on the hunt for magic bullet molecules -- single drug therapies that derail disease by attacking a specific cellular target. Despite the high profile success of drugs like Gleevec, which treats a form of leukemia by inhibiting the function of a single protein, the magic-bullet approach has fallen short in treating diseases caused by multiple cell defects or those affecting more than one type of cell, which is the majority of human ailments.

Doctors often rely instead on combination therapies, an approach that has proven successful in the treatment of cancer, infectious disease and neurological disorders. But new drug combinations typically are forged from chemical agents already known to be effective in treating a specific disease, a strategy that scientist Brent Stockwell says represents only a fraction of the combinations possible between currently approved drugs.

Stockwell's team at Whitehead Institute for Biomedical Research, in collaboration with scientists at CombinatoRx Inc. in Boston, Mass., recently reported the development of the first systematic approach to the discovery of novel combination drugs. Their approach uses high-throughput screens to rapidly identify combinations of compounds that pair synergistically to produce a desired therapeutic effect.

Remarkably, the researchers identified several novel pairings with significant therapeutic promise, including a new combination that kills an infectious, drug-resistant strain of the yeast Candida albicans while leaving human cells unharmed.

"Clinical results tell us that multi-component therapeutics often are successful in treating complex diseases," said Stockwell. "This method enables us to unlock an enormous set of potential therapeutic combinations that, left to traditional methodology, may have never been discovered."

Results from this study were published recently in the journal Proceedings
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Contact: Kelli Whitlock
newsroom@wi.mit.edu
617-258-5183
Whitehead Institute for Biomedical Research
15-Jul-2003


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