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NIH grant aids Creighton researchers in battling TB

Justin Tolman, PhDAn old drug may have new applications and implications in the worldwide fight against tuberculosis, according to the research of two Creighton University scientists in the School of Pharmacy and Health Professions.

Justin Tolman, PharmD, PhD, and Jeffery North, PhD, are participating in a two-year, $600,000 grant from the National Institutes of Health to determine the potential for the antibiotic clofazimine — synthesized 65 years ago, currently only used for the treatment of leprosy and also known for a bevy of adverse side-effects including severe nausea and skin discoloration — to combat TB, especially as more drug-resistant strains of the disease arise.

“Around the world, we’re becoming very concerned about the treatment options, given how more and more of the drugs currently used are becoming ineffective,” said Tolman, who specializes in pharmaceutics and pharmacokinetics. “Clofazimine is what you might call a ‘bad drug,’ but we’re seeing if we use it in a new way, it has the possibility to be effective against tuberculosis.”

The NIH grant stems from a study Tolman and North undertook with the aid of a Jack & Lois Wareham Faculty Research Award, in which they improved upon the results of a paper that showed clofazimine, when inhaled rather than taken orally, is effective against a mouse model of tuberculosis.

Graduate students in North and Tolman’s laboratories worked on preliminary studies and, late in 2018, the NIH was intrigued enough to award the grant to Tolman and North, working jointly with an engineering firm in New Hampshire developing an inhaler device to deliver the drug. With promising results, the researchers hope this summer to begin trials in healthy mouse and rat models to observe how the drug is working in the lungs, whether it spreads to other parts of the body, and what other effects it might have on organ function.

Confident all will go well, Tolman said the researchers hope to apply for the next phase in the NIH grant process, a three-year, $1.5-million package that includes testing their findings with mice infected with TB.

“So far, everything is progressing very well,” Tolman said. “The thing I’m most interested in is a bit of data that’s not been reported on to date in the pharmacokinetic literature: does clofazimine stay in the lungs or does it move to the rest of the body? Once we know that, it’ll answer a whole bunch of questions.”

While North has spent much of his career in TB research, it’s a new foray for Tolman, though he has a background in working with lung infections, especially hospital-acquired infections of a fungal nature. He says he remembers working with drugs like clofazimine as a graduate student.

“Taking another look at it this way has been interesting,” he said. “I’m also glad to be looking at tuberculosis. It’s a serious infection and a major cause of death around the world. If we can find ways to kill the TB bacteria and get answers about effective treatment, that’s what we’re hoping we can do.”


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