Pain drug kills resistant tuberculosis

Researchers at Weill Cornell Medical College have discovered that an off-patent anti-inflammatory drug kills both replicating and non-replicating drug resistant tuberculosis in the laboratory.

“Existing drugs are slow to eradicate Mycobacterium tuberculosis in patients and have failed to control tuberculosis globally,” wrote Carl F. Nathan, chairman of the Department of Microbiology and Immunology, the R.A. Rees Pritchett Professor of Microbiology, and the director of The Abby and Howard Milstein Program in the Chemical Biology of Infectious Disease at Weill Cornell, and his research team in their article published online September 10 in the journal Proceedings of the National Academy of Sciences of the United States of America.

The team set out to identify drugs that can kill Mycobacterium tuberculosis in the face of replication-inhibiting conditions. They discovered that an inexpensive, off-patent NSAID, oxyphenbutazone (Tandearil), can kill drug resistant tuberculosis. They found that the conditions that allow the bacterium to remain dormant modify the drug to the point that it starts reacting against both non-replicating and replicating forms of the disease. Their findings point to a potential new therapy for the more than 500,000 people worldwide whose disease has become resistant to standard drug treatments, the researchers note; however the drug may never be tested in clinical trials.

Oxyphenbutazone went on the market as a patented drug for arthritis-like pain in the early 1950s, and lost its patent and market dominance by the 1970s, the researchers said.

"It is difficult today to launch clinical studies on a medication that is so outdated in the United States, that it is mainly used here in veterinary medicine to ease pain," Dr Nathan said in a statement from the college. "No drug firm will pay for clinical trials if they don't expect to make a profit on the agent. And that would be the case for an off-patent drug that people can buy over the counter for pain in most of the world."

The researchers are continuing to look at other compounds for their action against tuberculosis.

The study was supported by the Tuberculosis Drug Accelerator Program of the Bill and Melinda Gates Foundation and the Abby and Howard P. Milstein Program in Chemical Biology of Infectious Disease.