Researchers awarded NIH grant to revolutionize TB treatment

Stop Jeff North, Ph.D., if you've heard this one before: an indole-based drug and a tuberculosis protein meet in a laboratory. There's a brief interaction, then the drug skates merrily away while the protein is nowhere to be found.

It sounds like great news with the potential to revolutionize tuberculosis treatment the world over. The National Institutes of Health thinks so, too. Earlier this year, the NIH awarded North, an assistant professor of pharmacy sciences at Creighton University, Mary Jackson, Ph.D., lead researcher on the project and a microbiologist at Colorado State University, and Helen Zgurskaya, Ph.D., a biochemist at the University of Oklahoma, a four-year grant of $2,075,078 to further the research.

A course of anti-TB drugs typically takes six months in its shortest form, but this latest breakthrough by North and his fellow researchers might be able to significantly reduce the time it takes to get patients cured of the disease. The key, however, is finding out what exactly happens in the meeting between the drug and mycobacterial membrane protein large 3 (MmpL3).

"It's still a bit of a black box," said North, who began research into TB treatments more than five years ago as a researcher at St. Jude Children's Research Hospital in Memphis, Tenn., before moving to Creighton in 2014. "The drug and the bacteria come together, the drug comes out. The grant is looking at what happens in that interaction. We know the drug is shutting that protein down and that's having a beneficial effect. We now have to see how it's shutting that protein down. If we can see that, we can design new generations of drugs that could help in cutting down the time it takes to undergo a TB treatment."

North said in areas where TB is most pervasive, a six- or even 12-month course of treatment is not often feasible, based on the availability of drugs, medical professionals to administer them and social and environmental conditions.

Shortening the course of treatment could mean more people cured and a lower likelihood of drug-resistant strains of TB, a consequence emerging in people who have received only a partial course of treatment. Approximately 20 percent of drug-resistant strains of the disease occur in people who have been treated for TB at least once before.

"We've known for awhile we needed to find a drug with a new way to kill TB," North said. "If we can take six months and make that four months or even two months, we can greatly reduce the pill burden and lessen the impact of some of the other factors involved, something like a civil war or unrest that can make it hard to get treatment to patients."