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The company has a library of thousands of compounds–drugs approved in the United States and other countries, food additives, natural products, drugs under development by partner companies–that can be combined in millions of ways. Add to that the need to test multiple doses, and there are tens of millions of experiments to perform, says Borisy.

For each pair of compounds, CombinatoRx tests 36 dosages on several cell types. To test whether a combination has potential as a therapy for inflammatory diseases like arthritis, for example, researchers try the combination on white blood cells. They first stimulate the cells to mimic inflammatory disease, then administer the different dosages to the cells, and finally test for indicators of inflammation (such as signaling molecules that keep the immune system on alert). Data from these experiments are fed into a computer featuring software that determines whether the drugs have synergy and, if so, at which doses. If a combination shows promise, the company tests it in animals and then starts clinical trials.

In its search for therapies for cancer, metabolic disorders like diabetes, and neurodegenerative disorders like Huntington’s disease, the company performs similar experiments on fat, muscle, nerve, and prostate-cancer cells, among others.

CombinatoRx’s rheumatoid-arthritis and chronic-pain drugs will be entering another round of large phase II clinical trials later this year. When Borisy founded the company in 2000, he says, its approach was considered provocative. “Now we have shown that it really works in humans.”

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Credit: CombinoRx

Tagged: Biomedicine, cancer, drugs, disease, drug delivery

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