Off-patent pain drug can kill resistant TB
Researchers at Weill Cornell Medical College have found that an off-patent anti-inflammatory drug that costs around two cents for a daily dose in developing countries can kill both replicating and non-replicating drug resistant tuberculosis in the laboratory -- a feat few currently approved TB drugs can do, and resistance to those is spreading.
Their findings point to a potential new therapy for the more than 500,000 people worldwide whose TB has become resistant to standard drug treatments.
But the researchers worry that the effective drug, oxyphenbutazone, may never be tested in TB clinical trials.
Weill Cornell's Dr. Carl Nathan and his research team found what they call the "completely surprising" ability of oxyphenbutazone to kill drug resistant TB after testing thousands of approved drugs against the bacteria. This repurposing of agents already on the market can lead to quicker testing for new uses.
"This agent might help save lives if there was a way to test it in TB patients," said Dr. Nathan.
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.
"It is difficult today to launch clinical studies on a medication that is so outdated in the United States, that it is mainly used here in veterinary medicine to ease pain," said the study's senior author, Dr. 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.
"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," he stated.
He added that oxyphenbutazone, best known under the trademark name of Tandearil, does have some established toxicities, "and is not a drug you should take for aches and pains if a safer alternative is available."
But the drug's major toxicities appear to be less frequent than the major side-effects of the drug regimens that are currently used to treat TB, he noted.
Their findings have been published online by the journal PNAS.