Can repurposed cancer drugs counter bioterror threats?

The U.S. Defense Threat Reduction Agency (DTRA), which is part of the U.S. Department of Defense, has hired Mark Buller, Ph.D., professor of molecular microbiology and immunology at SLU, to explore antiviral activity in poxvirus infection. The DTRA works on solutions to protect members of the U.S. military and its allies from weapons of mass destruction.

The value of the contract to Buller could grow to as much as $980,000, depending on the actual cost of the work.

Buller will study whether two compounds that are the active ingredients in the FDA-approved oral cancer medicines Gleevec and Tasigna can prevent and treat monkeypox virus infections in a mouse model. Monkeypox is an orthopox virus that has similar characteristics to smallpox.

"The overall focus of this contract is to see which viruses would be susceptible and succumb to the medications and which would not," said Buller, who has studied orthopoxviruses since 1982. "The drugs we are studying already are licensed, which means there are fewer regulatory hurdles for approval for a different use."

After the 2001 terror attacks, the National Institutes of Health and Department of Defense increased funding research in counter-measures for orthopoxviruses and other dangerous pathogens that could be weaponized.

"They soon realized that they can't make unique anti-viral medications and vaccines for every potential weapon of mass destruction, and now are developing broad-spectrum anti-infectives that would be effective against many pathogens," Buller said.

Gleevec and/or Tasigna may be examples of broad-spectrum anti-infectives as research has shown they inhibit replication of at least three distinct viruses.

Scientists are studying Gleevec and Tasigna because they target the same enzyme that vaccinia virus and ebola virus require in their natural life cycle. The goal is to halt infection or to slow down the spread of the virus so the body's own immune system has enough time to mount a strong defense against the virus. Researchers at other institutions are studying the effectiveness of Gleevec and Tasigna against alphaviruses, arenaviruses, bunyaviruses, filoviruses and flaviviruses.