Macrolide drug class extended to treat TB

October 21, 2004

A class of drug, which is currently used to fight respiratory tract infections, has demonstrated pharmacological features and potential antibacterial drug activity that may prove effective against Tuberculosis, which is currently experiencing a worldwide resurgence.

Under a two-year research development program, the macrolide class of drugs will be the subject of focus as researchers attempt to synthesize and optimize macrolide derivatives for the TB indication with verification of in vitro activity against clinical isolates.

The primary goal is to optimize the anti-TB activity of macrolide antibiotics through the synthesis of additional chemically modified erythromycin derivatives. Erythromycin is a good foundation for this project since it is an affordable starting material and could pave the way to engineer new, low-cost TB drugs.

The program is a project between The Global Alliance for TB Drug Development (TB Alliance) and the University of Illinois at Chicago (UIC) College of Pharmacy. The research is to be carried out at the Ramathibodhi Hospital, Bangkok, Thailand, as high incidences of drug resistant TB in the country make it an ideal location.

Dr. Zhenkun Ma, Head of Research, at the TB Alliance told DrugResearcher.com: "Macrolides have been optimised extensively for the treatment of respiratory tract infections and now, we will be able to optimise macrolides for the treatment of tuberculosis."

"Macrolides are a natural product, produced by bacteria itself and has demonstrated potent activity against gram positive bacteria. Its orally active pharmacokinetics, make it an ideal drug for use in children."

A spokeswoman for the TB Alliance said that while the technology and the quality of the drug were key factors, it would be unlikely the market would see a new treatment for TB within the next ten years.

Current antibiotics used in TB treatment are based on research conducted over 30 years ago, and the most potent drug, rifampicin, was introduced in 1965. According to recent estimates published by the Infectious Disease Society of America, today's global pipeline of antibiotics amounts to only five compounds in clinical development, out of a total of 506 potential new drugs for all indications.

"TB is what is known as a neglected disease, of which no new drug specific for the disease appearing in the pipeline for forty years. One reason is financial, with big pharmaceutical companies leaving TB R&D because of its relative lack of profitability," the spokeswoman added.

Ma added: "This makes this discovery even more important. Drug resistant TB is a problem that is getting bigger. The absence of new drugs only adds to this problem of which this research program is trying to address."

Release of findings from the latest World Health Organization report on multi-drug-resistant strains in tuberculosis revealed a total of 300,000 cases, most existing where HIV is spreading fastest. 79 per cent of MDR TB are "super strains" resistant to 3 of 4 first-line drugs. The report also stated that TB patients in Eastern Europe and the former Soviet Union are 10 times more likely to have MDR-TB.