Wednesday, 2 July 2008

Anticancer drug developed from Aspergillus fumigatus

The Harvard team
Fumagillin is a secondary metabolite of Aspergillus fumigatus and belongs to that much-feared and maligned group of substances associated with fungi - mycotoxins.

This report follows the story of the discovery that this toxin might be useful.

First came a stroke of luck (and the ability to take advantage of that luck) reminiscent of the story of Fleming's discovery of penicillin.

"The fungus was discovered by Harvard’s Donald Ingber by accident while trying to grow cells that line blood vessels, or endothelial cells. The cells were affected by the mold in a way that prevented the growth of small blood vessels called capillaries."

The 'mycotoxin' was found to 'toxic' towards cancerous tumours as it prevented the growth of blood vessels in tumours, thus limiting their ability to grow (an activity referred to as anti-angiogenesis).

Having recognised this tremendously useful property a man-made version of the metabolite (TNP-470) was developed in the early 1990's by a company in Japan in an attempt to develop an anticancer drug. Unfortunately it was not successful:

"the drug would not stay in the body for very long and required continual infusions. It also affected the patients’ brain causing dizziness, depression, and other side-effects. Takeda Chemical Industries dropped it."

Years later we have developed the technology to encase drugs in molecular capsules that prevent them being broken down via stomach acid. An encapsulated version of TNP-470 was developed (now called to as Lodamin) and now it was found to be absorbed by the intestines and then go straight to the liver with no sign of side effects in mice.

Tests on mice show good activity against aggressive liver tumours but there are no reported results in humans yet.

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