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Old Drug, New Use (Again)

Malaria is one of the nastier scourges confronting humankind. The lowly mosquito carries and spreads the protozoan responsible for the disease; each year over two hundred million new infections occur worldwide, killing over three quarters of a million people. There are useful treatments, principally drug combinations based around artemisinin. Severe malaria is responsive to quinine, but lest you think you can get your dose via imbibing gin and tonics, the preferred route is intravenous or intramuscular.

The grand challenge for treating malaria, as it is with all infectious diseases, is drug resistance. A recent paper by a high-powered collaboration between the NIH and Columbia University rises to this challenge. The authors took a chemical library of 2816 compounds approved for treating all manner of human diseases, and screened them against 61 parasite cell lines. Thirty-two drugs emerged that were highly active against at least 45 parasite lines. Some were known to have anti-infective capacities, but surprisingly, many were not – including drugs used to treat cardiovascular, hypertensive, and neurologic diseases.

The scientists then examined the cell lines’ entire genomes to see which genes varied among the parasite that might explain drug sensitivity. Again surprisingly, just three genes accounted for much of the way in which antimicrobials influence parasites. The result suggests that combinations of drugs that separately target these different gene products may provide a route to slowing the emergence of drug resistance.

This study links chemistry with molecular biology in a novel way that provides new avenues for developing treatments for malaria. And like all good science, the approach is extensible in principle to other infections and thus offers some considerable optimism for future antimicrobial drug development.

Tom Tritton is President and CEO of CHF.

Related:
Old Drug, New Use [Periodic Tabloid]
Bad Air [Chemical Heritage]

Posted In: Technology

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