The College of Veterinary Medicine and Biomedical Sciences tuberculosis research program has received two grants from the Bill & Melinda Gates Foundation to assist in the development of tuberculosis drugs.
The two grants - one for $2.6 million and one for $1.1 million - will streamline and identify the best drug-testing methods and advance basic knowledge about how the bacteria that causes tuberculosis functions in a living host. The grants are part of a larger $280 million commitment from the Gates Foundation to accelerate the development of new drugs, vaccines and diagnostics for tuberculosis.
The $2.6 million grant will fund exploration of how the mycobacterium that causes tuberculosis grows and interacts in a laboratory compared to inside a living human or animal host. Scientists currently screen potential new drugs in cultures in a laboratory - an artificial environment where important and realistic environmental factors that would interact with the bacteria are missing.
"In a living host, the presence of bacteria changes the metabolism of the lung. In turn, the lung environment likely changes the metabolism of the bacteria," said Dr. Dean Crick, an Associate Professor and research project co-leader in the Mycobacterium Laboratories, Department of Microbiology, Immunology and Pathology (MIP). "We don't know much about how the bacterial metabolism is altered in response to the host's defenses, making it difficult to replicate a realistic environment in a laboratory."
Researchers do know that the bacteria and the lung constantly interact and the environment consistently changes on a chemical basis. For example, bacteria feed on the lung, but researchers don't know exactly what they feed on or how that changes over time.
"Better understanding of how a disease state environment interacts with the bacterium that causes tuberculosis will help drug researchers improve their drug development and testing approaches," said Dr. John Belisle, also a Professor in MIP and research project co-lead researcher on the grant.
The $1.1 million grant will help mycobacterium researchers sort through laboratory testing systems currently used to study the effectiveness of potential drugs and gain an industry consensus among the world's 20 TB drug research organizations on which laboratory tests are the most effective. In addition, the group will do an extensive review of historical TB research to look for useful research details and testing methods that may have been lost over time. Streamlining this system also will help laboratories in universities and the industry more accurately compare information on their search for an effective drug or drugs.
"With a growing urgency, the fight to develop drugs to treat and prevent tuberculosis has become increasingly important as the bacterium that causes the illness mutates," said Dr. Anne Lenaerts, the primary researcher on the drug model comparison grant. Dr. Lenaerts is an Assistant Professor in MIP. "An organized preclinical testing system among the tuberculosis community that is devoted to finding treatments will help to more quickly advance our research into results that can save lives."
A drug that treats tuberculosis in a novel way has not been developed in decades, and the bacterium that causes the disease continues to mutate to become resistant to current drug approaches. About 9 million people are infected with TB each year and 2 million die. Of the 9 million new cases each year, close to a half million are resistant to multiple drugs that once were effectively used to treat the disease. In 1993, the World Health Organization declared TB a global health emergency, a situation that continues today.
