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Compound J tackles tuberculosis

December 9, 2004 By Emma Marris This article courtesy of Nature News.

Next generation of drugs perform well against resistant strains.

Tuberculosis kills 2 million people a year, but a promising drug may save some of them, if it makes it to the clinic. The compound has a different mode of action from existing therapies so it acts more quickly, and works on patients whose infections are resistant to today's drugs.

One-third of the world's people carry the bacteria that cause tuberculosis (Mycobacterium tuberculosis); the microbes are kept at bay by the immune system so carriers don't feel sick. But when the immune system takes a hit, from AIDS, for example, the bacteria can multiply and cause the fatal, bloody coughing of tuberculosis.

In future, people may call the next few years a revolution in tuberculosis drugs.
Mel Spigelman
Global Alliance for TB Drug Development, New York
The current course of antibiotics takes half a year, and patients start to feel better early on, so many abandon the pills before they have killed all the bacteria. The few organisms that survive are those most resistant to the medicine. They multiply and spread, and when they next make a person sick, they are much harder to kill.

A new drug, currently called 'compound J', has been shown to kill M. tuberculosis twice as effectively as standard antibiotics in mice. This means a course of pills would be shorter and easier to complete.

In addition, the way that the compound attacks the bacteria is completely different, so no patients will have resistance to it yet. The drug is introduced online in this week's Science by a group of Johnson & Johnson researchers and external collaborators, led by Koen Andries at Johnson & Johnson in Beerse, Belgium1.

To the source

I never came across such a drug with so many positive properties at this stage in development.
Koen Andries
Johnson & Johnson in Beerse, Belgium
The molecule works effectively because it moves easily to the lungs, where the multiplying bacteria must be stopped in their tracks. There, it cripples a bacterial enzyme called ATP synthase, preventing it from assembling ATP, the little packets of energy that allow cells to work.

Human versions of the synthase are not affected by the drug and initial studies in humans show that injections are safe, at least for short periods of time. Trials in people who are actively sick are now under way, although it will be many years before the drug makes it to the market.

When it does, it may especially benefit those with both tuberculosis and HIV. One of the drugs in the standard tuberculosis cocktail does not mix well with many HIV drugs, but a regimen with compound J would be fine. Another potential bonus is that the compound may be useful against latent tuberculosis, as it kills even when the bacteria are not actively reproducing.

Positive properties

"It's a fantastic compound," says Andries. "I never came across such a drug with so many positive properties at this stage in development."

Although no new tuberculosis drugs have joined the market for 40 years, other compounds are in various stages of development. Mel Spigelman, research and development director at the Global Alliance for TB Drug Development in New York hopes to see a wholly new drug combination within the next decade.

"This really is a nice advance in the field," Spigelman says of compound J. In future, people may call the next few years "a revolution in tuberculosis drugs," he adds.


  1. Andries K., et al. Science, doi:10.1126/science.1106753 (2004).


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