NEW YORK (Dec. 12, 2007) -- Weill Cornell Medical College has received two grants totaling $2.4 million from the Bill & Melinda Gates Foundation to help fight tuberculosis, an epidemic that infects one-third of the world's people and kills nearly two million yearly -- mostly in the poorest countries.
The grants will support research towards developing innovative TB drugs that are more effective than current treatment options. Even the best available TB drugs require difficult and lengthy regimens and are increasingly losing their effectiveness; last year there were more than 400,000 cases of drug-resistant TB. In addition, there is a need for faster-acting TB drugs; current drugs must be taken for at least six months to be fully effective. Many patients, for various reasons, do not complete the full course of treatment, which leads to the development of drug-resistance in Mycobacterium tuberculosis, the organism that causes TB.
"We are very grateful to the Gates Foundation for supporting our efforts to fight tuberculosis," says Dr. Antonio M. Gotto Jr., the Stephen and Suzanne Weiss Dean of Weill Cornell Medical College. "This important work is also made possible using the advanced technology available at our Abby and Howard P. Milstein Chemistry Core Facility, which opened last year."
"These grants support research focused on testing many existing chemical compounds for their potential ability to kill or interfere with the organism that causes TB. We already know of and use some compounds that kill or weaken TB pathogens when they are in the replicating phase. Being able to kill TB organisms in their non-replicating phase, which represents most of their existence, will be key to shortening curative TB therapy from the current six months (or longer) to perhaps just a couple of weeks," says Dr. Carl. F. Nathan, chairman of the Department of Microbiology and Immunology, and R.A. Rees Pritchett Professor of Microbiology at Weill Cornell Medical College, and director of the Abby and Howard P. Milstein Program in Chemical Biology. "Finding those effective compounds may also mean more effective therapies for the emerging drug-resistant forms of TB." Dr. Nathan is a principal investigator on one of the two Gates Foundation grants.
Dr. Nathan and his colleagues have helped to shape our basic understanding of innate immunity and host-pathogen interactions. He introduced the concepts of cytokine-mediated activation and deactivation of macrophages, helped identify the first macrophage activating factor (interferon-g) and its therapeutic potential, demonstrated the role of the respiratory burst in macrophage biology, and pioneered numerous advances in inducible nitric oxide synthase (iNOS), which plays a key role in the immune system. These contributions inform current research efforts, including those directed at macrophage interactions with Mycobacterium tuberculosis.
"These grants will also help us to demonstrate to drug companies a safe way to screen hundreds of thousands of chemical compounds against the TB organism so the companies can do it themselves," says Dr. Nathan. "Right now very few drug companies have the special core facilities needed to do such work without risk of infection."
Dr. Dirk Schnappinger, associate professor of microbiology and immunology at Weill Cornell Medical College and principal investigator on one of the Gates Foundation grants, and colleagues are focused on multidisciplinary work in functional genomics, molecular genetics and biochemistry aimed at understanding the contributions of individual genes in M. tuberculosis. They have developed systems that allow silencing of mycobacterial genes in vitro and during macrophage infections. They are using these systems to evaluate the role of specific genes that seem important for the survival of M. tuberculosis within the host. These studies should provide proof-of-principle for the hypotheses that gene silencing can be used to: 1) identify biological processes that are essential for growth and persistence of mycobacteria during infections in the mouse; 2) genetically mimic the action of antibiotics on the progression of M. tuberculosis infections and thus aid the prioritization of drug targets; and 3) study the function of essential genes using functional genomics.
Dr. Nathan's and Dr. Schnappinger's grants are two of 11 new grants, totaling $280 million, by the Gates Foundation to speed research and development on promising vaccines, diagnostic tests and treatments to help reduce the global TB burden.
|Contact: Andrew Klein|
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College