IU researchers find new way to fight tuberculosis

Tuberculosis might not be an illness many Americans are exposed to, but Zhong-Yin Zhang, chairman of the IUPUI Department of Biochemistry and Molecular Biology, said it is the most prevalent infectious disease in the world.

Thanks to new discoveries by a team of IU researchers led by Zhang and supported by grants from the National Institutes of Health, the time it takes to cure tuberculosis may be substantially abridged, potentially leading to a significant reduction in the number of TB cases worldwide.  

As much as one-third of the global population is afflicted with TB and nearly 2 million die per year from the infection. Zhang said the drugs used for treatment have remained unchanged for nearly 60 years and require six to nine months of regimented medication. The explanation for this is an economic one, he said.

“Most pharmaceuticals are out of the anti-infectious disease business because it isn’t very profitable,” Zhang said. “You get an infection, you take a pill, and you’re cured ... and you stop taking it. Whereas if you’re taking Lipitor for high cholesterol, you take it until you die.”

The void left by pharmaceutical corporations in TB research is filled by academic researchers, he said.    

The innovations developed by the research team center around microphages, cells in the immune system that help defend the body against infectious bacteria.   

Zhang said they found TB is able to live and survive within microphages and secrete an enzyme called mPTPB that disrupts pathways used to fight off harmful bacteria.

“It basically impairs and subverts the host’s immune system so that it can survive and proliferate,” he said.

By inhibiting the TB bacteria from releasing mPTPB, the disease is no longer able to exist within the microphages and dies.

The breakthrough for the IU research group came when they successfully created a molecular compound that is able to block the secretion of mPTPB and then kill the TB bacteria in the microphage.   

Zhang said if this molecule inhibitor is able to develop into a drug, it could eliminate TB from the body within one month.

“Basically, we can accelerate the treatment,” he said. “So if this were to really become a drug, it would be a big thing.”

Gyanu Lamichhane, assistant professor of medicine at the Johns Hopkins Department of Medicine, said the current medication for TB definitely cures infected patients, but it does so in a cumbersome amount of time.

“Think about it,” he said. “You start taking the drug and if in two weeks you feel fine, are you going to take it for six months?”

It’s more than just a matter of convenience, however. If a TB patient does not complete the six-month treatment, much of the TB bacteria escapes the effects of the drug and begins growing again with a new and powerful resistance to the medication, Lamichhane said.

Qi-Zhuang Ye, associate professor in the Department of Biochemistry and Molecular Biology at the IUPUI School of Medicine, noted that this is one of the greatest challenges to eradicating TB.

“It’s not only the tuberculosis bacterium that is the problem,” he said. “The major problem is that more bacteria are becoming drug-resistant. This makes TB even more difficult to treat.”

The benefits of accelerating the recovery process to one month are twofold: the patient is more likely to finish the treatment and the TB’s resistance to anti-bacterial drugs will diminish, Ye said.

Although Zhang said the TB-fighting compound discovered by his IU research team is not a drug yet, it is well on its way to becoming a viable treatment for the disease.

IU recently patented the molecule inhibitor and has licensed it to a start-up company in Indianapolis called Arden. Zhang said if the next phase of animal testing goes well for the newly discovered compound, Arden will play a big role in pushing the molecular compound into the marketplace for drug development.   

Lamichhane said 2010 will see the highest number of TB deaths in history due to the HIV/AIDS epidemic in Africa and the poor quality of life in developing countries. He said those with HIV are much more likely to become infected with the disease.  

Because it is the poor and powerless that experience the brunt of TB, there’s little motivation among corporate health-care institutions to seriously pursue effective treatment and invest in substantial research, Lamichhane said.

“It’s really tough because the disease doesn’t kill people with resources,” he said. “We tend to forget the resource-less and unfortunate people, and we don’t think they’re a part of our society, while here we are living in this global village.”