OREGON STATE UNIVERSITY

OSU receives Gates Foundation grant of nearly $1M for tuberculosis research

09/25/2008

CORVALLIS, Ore.— Oregon State University biomedical researcher Luiz Bermudez, M.D., has received a grant of nearly $1 million from the Bill & Melinda Gates Foundation to study a potential new treatment for tuberculosis (TB), a contagious disease that afflicts approximately one third of the world's population

While TB is curable, approximately 1.5 million people die from the disease every year, and drug-resistant strains are on the rise, according to the World Health Organization. The Gates grant will allow Bermudez, an infectious disease expert with more than 25 years experience in TB research, to study how a common treatment for malaria called mefloquine may also be used to treat tuberculosis.

"Tuberculosis is a major health issue. This research could lead to a very quick way to find a new therapy," said Bermudez. "If this project is successful, it could substantially improve the care of patients with tuberculosis."

A bacterial disease which usually affects the lungs and can be spread through the air, tuberculosis can be fatal if left untreated. The majority of TB infections occur in developing countries where patients face challenges completing the required six months of treatment, contributing to the emergence of new, drug-resistant strains.

"There is an urgent need for more fast-acting, effective drugs to treat TB," said Dr. Ken Duncan, Senior Program Officer at the Gates Foundation. "By supporting promising work such as the mefloquine investigation at OSU, we hope to add new weapons against drug-resistant strains and improve our ability to fight TB."

The Gates Foundation grant of $955,000 will support two years of the project led by Bermudez, a microbiology professor and the head of the College of Veterinary Medicine's biomedical sciences department. The project will also involve OSU pharmacy professor Mark Zabriskie as a co-principal investigator as well as three post-doctoral assistants.

"This research addresses a significant public health concern and has the potential to save lives around the world," said Cyril Clarke, dean of the College of Veterinary Medicine. "Dr. Bermudez is a leading researcher in this field and has made many major breakthroughs that have improved our understanding of tuberculosis."

Bermudez and his group first discovered that mefloquine could kill the mycobacteria that cause tuberculosis six years ago while conducting a drug screening study funded by the National Institutes of Health to find existing medicines that are effective against all types of mycobacteria.

While mefloquine is in use today as a malaria treatment--Bermudez himself took it before a trip to Africa--it produces side effects in some people. This toxicity inhibits its use against tuberculosis, which requires a more frequent and extended treatment than malaria. However, since the potential of mefloquine was discovered, Bermudez and other researchers have isolated a compound within the drug, called an isomer, which does not exhibit the same toxicity.

Before this compound can be developed into a TB treatment, Bermudez needs to know exactly how mefloquine works against tuberculosis. The efficacy of mefloquine against TB, however, has actually hindered its further development as a treatment. Usually, researchers can create a strain of a bacterial disease that is resistant to a new drug to find out exactly which part of the organism it targets.

So far, Bermudez' team has been unable to create a mycobacterial strain that is resistant to the mefloquine, which suggests that either it is so fatal to the TB mycobacteria that it kills the organisms before they can adapt, or that it has multiple targets. As part of the Gates Foundation grant, Bermudez plans to use state-of-art genomic and proteomic methods to find the target of mefloquine and the individual compounds that make up mefloquine.

"The Gates Foundation grant will help us investigate what the target is for mefloquine," said Bermudez. "If we find the target or targets, we will be able to design a new class of compounds that will kill the bacteria."