An award of a Bill and Melinda Gates Grant to Colorado State University’s tuberculosis research program will allow scientists to continue pursuing new discoveries including a new finding that questions long-held beliefs about how tuberculosis often reoccurs in a person with the infection and why traditional tuberculosis treatments work so slowly.
The $1.25 million grant, part of the Gates organization’s initiative to develop faster and more effective tuberculosis treatments, was awarded to Ian Orme, professor in the Department of Microbiology, Immunology and Pathology in the College of Veterinary Medicine and Biomedical Sciences.
The grant allows Orme and his team of researchers to pursue the ever-present question facing tuberculosis researchers regarding why it takes nine to 12 months of antibiotics to kill tuberculosis and why, even after such extensive treatment, many patients relapse.
"We think it is because current drugs cannot reach all of the tuberculosis bacterium in an effective manner," Orme said. "We know that it kills about 90 percent of the bacteria within the first few weeks of treatment, but the remaining 10 percent persists and is very hard to kill. As yet we know extremely little about these persistent bacteria. But we think we may have now discovered how it might be hiding from the drugs."
Orme’s research team at Colorado State has new data that shows the persistent bacteria can be found in very discrete areas within lesions in the lung. The bacterium may also exist in a state that tuberculosis experts have previously not considered: the bacterium may be forming microscopic clusters in a biofilm. A biofilm is a thin layer of material that encapsulates the bacterium and protects it from outside elements – in this case, those elements include medications aimed at killing the bacteria. Tuberculosis researchers around the world have only recently begun to suspect that the tuberculosis bacterium can form a biofilm. Orme’s research team now has new information suggesting that the biofilm forms about two to three months after infection.
According to Orme, because the drugs cannot get to the bacterium that causes tuberculosis, the persistent bacteria remain in the host and cause relapses after treatment is completed.
The Gates Foundation grant will fund a closer look by Orme and his team at the area of tissue in the lungs where these bacteria hide, to see if new drugs can kill the persistent bacteria before the biofilm forms or alternatively disrupt the formation of the biofilm to prevent it from protecting the bacterium.
"Infectious disease research is absolutely essential to creating a better understanding of how diseases such as tuberculosis attack the human body," said President Larry Edward Penley. "Healthy populations are essential to a healthy, sustainable planet. Through this greater understanding of such diseases, we will be able to advance treatments that can someday be the salvation of millions of people worldwide who suffer from devastating illnesses that have enormous personal and societal costs."
"Colorado State University’s tuberculosis research and Dr. Orme’s research program are international leaders in working to find fast and effective cures and preventative measures to help millions of people suffering from tuberculosis," said Colorado State University Provost Tony Frank. "This grant will help advance important work toward advancing promising discoveries that may help scientists more quickly treat people with this disease."
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 to research tuberculosis drugs today, including specialized tests that facilitate screening large numbers of compounds within shorter time frames.
Developing treatments for tuberculosis is a lengthy process. Before reaching human trials, potential drug compounds are tested first in the laboratory against the bacterium that causes tuberculosis.
Tests for toxicity and to determine how well the drugs are absorbed by the body follow. Subsequent testing includes determining if drugs reach the blood stream adequately, then tracking how well they travel to and penetrate targeted cells in the lungs. Finally, the compounds are scrutinized 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 and develop resistance to current drug approaches. About 9 million people are infected with TB each year, and 2 million die annually from the disease. Of the 9 million new cases each year, more than a half-million are now resistant to multiple drugs that once effectively treated the disease.
In 1993, the World Health Organization declared tuberculosis a global health emergency, a situation that continues today.
Colorado State University, an international leader in infectious disease research, is home to the Rocky Mountain Regional Biocontainment Laboratory, funded by the National Institutes of Health, and the Rocky Mountain Regional Center of Excellence in Infectious Disease, also funded by the NIH. The university is among the world’s leaders in researching West Nile virus, drug-resistant tuberculosis, yellow fever, dengue, hantavirus, plague, tularemia and other diseases. The new Regional Biocontainment Laboratory provides the university with improved and safer equipment to research ways to protect the United States from bioterrorism and emerging diseases such as avian influenza. Researchers will investigate and develop new treatments and vaccines to protect against these agents.
Infectious disease 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, which are alliances of academic researchers, economists and business experts that encourage collaboration and bridge the vastly different worlds of business and academia. In the last few years, Colorado State has received millions in grants for infectious disease research, including research in the Infectious Disease Supercluster.
Infectious disease research programs receive roughly $40 million in annual research funding in such key areas as mycobacterial diseases, vector-borne diseases, prion diseases, food safety, plant pathology, and biodefense and emerging pathogens.