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Colorado State University’s esteemed tuberculosis research program today received two grants from the Bill & Melinda Gates Foundation to facilitate the development of tuberculosis drugs. The grants, with a combined amount of $3.7 million, will fund important areas of research that have previously been under-funded.
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.
"These grants will further help Colorado State develop life-saving measures against one of our world’s most persistent health challenges," said Colorado State President Larry Edward Penley. "Our tuberculosis research program is known internationally for its leadership in this effort, and we are proud to receive these grants from the Gates Foundation to fight infectious diseases around the globe."
A $2.6 million grant will fund exploration of how the bacteria 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. Researchers have not understood those changes because adequate basic research into these interactions has not been conducted.
"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 Dean Crick, an associate professor and research project co-leader on the grant, which was given to the Microbiology, Immunology and Pathology department in the College of Veterinary Medicine and Biomedical Sciences. "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 John Belisle, also a professor of Microbiology, Immunology and Pathology and research project co-lead researcher on the grant.
Another $1.1 million grant will help Colorado State researchers sort through a plethora of different laboratory testing systems currently used to study the effectiveness of potential drugs and gain an industry consensus among about 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 will also 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 bacteria that causes the illness mutates," said Anne Lenaerts, the primary researcher on the drug model comparison grant. Lenaerts is an assistant professor in Microbiology, Immunology and Pathology. "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."
While government agencies typically fund basic tuberculosis research, funding dollars often run short in areas that need attention. The Bill & Melinda Gates Foundation asked for proposals from TB drug researchers after extensively examining problems that hinder tuberculosis drug development.
The resulting plan asked researchers to propose ways to address gaps identified as slowing down drug development. The gaps cover areas where research could make a difference in drug development, which are typically not funded or are not attractive to fund, but are hampering drug development.
"We are quite honored to receive two grants from the Bill & Melinda Gates Foundation," said Dr. Lance Perryman, dean of the College of Veterinary Medicine and Biomedical Sciences. "Our tuberculosis program makes a significant impact as a leader in tuberculosis drug development. This funding will help us tackle two important problems facing that field today and advance a goal we share with the Gates Foundation of saving millions of people from suffering from tuberculosis."
For the past 10 years, Colorado State University has managed the National Institutes of Health’s drug compound testing program for tuberculosis. The university’s Department of Microbiology, Immunology and Pathology, part of the College of Veterinary Medicine and Biomedical Sciences, has tested more than 85,000 potential drug compounds since 1997. The university tests new compounds being investigated as potential TB treatments by other universities and by pharmaceutical companies. Compounds being looked at by pharmaceutical companies, other universities and Colorado State researchers are tested in the program.
The university has developed numerous tests and models used to research TB drugs today, including specialized tests that facilitate screening large numbers of compounds within shorter time frames.
Developing drugs for tuberculosis is a lengthy process. Before they reach human trials, potential drug compounds are tested first against the bacterium that causes tuberculosis in a test tube. Tests for toxicity and tests to determine how well they are absorbed by the body follow. Subsequent testing includes tests to determine if they reach the blood stream adequately, then to track how well they travel to and penetrate targeted cells in the lungs. Finally, the compounds are tested for their effectiveness at lowering the amount of bacteria in the lungs. Between each round of testing, which can last for several weeks or months, the potential drug compounds are refined by chemists and retested. A potential compound may repeat one level of testing multiple times because of these chemical refinements.
A drug that treats tuberculosis in a novel way has not been developed in decades, and the bacteria 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.
"These grants are testaments to the extraordinary work being done by our faculty to advance our knowledge and treatment of this terrible disease – and to the need for our infectious disease Supercluster, which will help Colorado State get the results of this research to market more quickly," said Senior Vice President and Provost Tony Frank.
Tuberculosis is a focus of Colorado State University’s MicroRx, a first-of-its-kind enterprise to speed the transition of life-saving research on infectious diseases from the academic world into the global marketplace. MicroRx, unveiled in February, is just the first of the university’s Superclusters – alliances of academic researchers, economists and business experts designed to encourage collaboration and bridge the vastly different worlds of business and academia.
Since the 1960s, Colorado State University has engaged in infectious disease research and today is a world leader in researching vaccines, diagnostic tests, medications and ways to prevent the spread of infectious disease. Colorado State’s Foothills Campus, a global complex devoted to infectious disease research, is supported by more than $200 million in research funds from entities including the National Health Institute, Centers for Disease Control, NASA, Department of Homeland Security and the U.S. Department of Agriculture.