National Institutes of Health (NIH) Awards Seven Year Grant to Tackle World Health Problem
In an effort to stop tuberculosis (TB) from becoming progressively less treatable worldwide, the NIH (the US Government’s medical research agency) has awarded Weill Cornell Medical College more than $6.2 million in first-year funding to support a research collaboration among six institutions in close alliance with voluntary pharmaceutical partners. The total funding, provided by the National Institute of Allergy and Infectious Diseases, could be up to $45.7 million over seven years.
TB-causing bacteria are increasingly becoming resistant to the most commonly used treatments, presenting a growing problem in a globalized world, says TB Research Unit principal investigator Dr. Carl Nathan, chair of the Department of Microbiology and Immunology at Weill Cornell. For patients who don’t respond to those drugs, the infection can require more than two years of therapy with multiple, toxic and expensive alternatives, which often fail. When TB, which is spread through the air, is not effectively treated, it is usually lethal.
“Neither academia nor pharma can solve this problem working alone. We have to work together to improve treatment of tuberculosis, or it will continue to spread and become even more resistant to treatment than it is today,” says Dr. Nathan.
Infectious disease specialist, Dr. Michael Glickman, who is serving as the TB Research Unit’s co-principal investigator, notes that TB is the single leading cause of death from bacterial infection, and the second leading cause of death from any pathogen. One in three people globally is infected with the bacteria that cause TB. In 2013, an estimated 9 million new cases of TB were reported and 1.5 million people died, according to the World Health Organization.
The Tuberculosis Research Unit involves two main tracks. The first addresses TB infection biology in patients, and the center of this work shifts to Haiti, where TB, including drug-resistant TB, is a major health problem. Dr. Glickman’s group will study the expression of genes by blood cells that may provide markers of resistance to initial infection and an early indication of treatment response. He will also investigate the effect of special types of lymphocytes and the role of composition of the intestinal bacteria in resistance to infection and response to therapy.
The second, parallel track of the grant, led by Dr. Nathan, continues and expands ongoing efforts by investigators at Weill Cornell and other institutions who have been working with the Bill & Melinda Gates Foundation’s TB Drug Accelerator. In that program, pharmaceutical companies provide chemical compounds that academic labs test in diverse ways, seeking compounds with new mechanisms of action. The active compounds, called “hits,” must pass through a gauntlet of increasingly stringent tests, often undergoing extensive chemical modifications, before they qualify as “leads” that can be considered for later stages of drug development.
In this “hit-to-lead” work, researchers seek the active compounds that are most potent and least toxic, try to identify their molecular targets, and test whether their properties can be improved. In particular, Dr. Nathan’s lab tests if the compounds can kill persistent TB bacteria. These tests were developed in response to ongoing studies of TB’s biology, including its genetics and the genetics of the host response, Dr. Nathan says.
Through the Drug Accelerator program and related collaborations, multiple drug companies have allowed Dr. Nathan’s team to screen more than 1.3 million compounds. Such open access to company compound collections “is almost unheard of,” says Dr. Nathan, “particularly when access is granted to the same academics by several companies at once.“
