Notre Dame researchers seek to identify new anti-tuberculosis agent

by Marissa Runkle

Marvin Miller

Marvin Miller, the George and Winifred Clark professor of Chemistry at the University of Notre Dame, has received a $1.9-million grant from the National Institutes of Health (NIH) to advance tuberculosis research. The epidemic tuberculosis infects an estimated 14.4 million people and kills some 4,500 every day. Many strains of the disease have become resistant to the standard treatment that involves taking multiple drugs for several months.

Miller and his research group aim to understand TB’s essential iron sequestration machinery to discover new targets and exploit this pathway for developing novel anti-TB agents. The synthesis of the iron sequestering siderophores from mycobacteria allows for the exploitation of a “Trojan Horse” drug treatment with new and existing drugs. The grant also will help the lab advance its current lead small molecule anti-TB agents, which are nanomolar inhibitors of drug-resistant strains, through in vivo pre-clinical development, patenting, and potential partnering with industry to bring new treatments to the marketplace.

More than four-fifths of TB cases are in Africa, Southeast Asia and the Western Pacific, although 12,898 cases were provisionally reported in the United States in 2008. The airborne bacterium that causes the disease can spread from person to person in close contact and can lie dormant for years. It kills mostly poor, HIV-infected, immunologically-compromised and elderly people. The standard treatment worldwide involves the administration of isoniazid, pyrazinamide, ethambutol and rifampin for two months followed by four additional months of rifampin and isoniazid.

“Armed only with long dosing regimens of antiquated drugs, we cannot hope to win the war against TB,” Miller says.

The lab’s TB research includes collaborations with researchers at the NIH, DowAgroScience, the Eli Lilly TB Initiative, as well as researchers in India, China and Germany.

Miller, co-founder of PracticaChem LLP, has more than 260 peer reviewed publications and 20 issued patents. He is a consultant to the pharmaceutical and biotechnology industries as well as an expert witness in medicinal and organic chemistry, synthesis and analytical interpretation.

Contact: Marvin Miller, the George and Winifred Clark professor of Chemistry, 574-631-7571,