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New Drug Beats Tuberculosis in Mice

If effective in humans, it may shorten treatment duration

THURSDAY, Dec. 9, 2004 (HealthDayNews) -- For the first time in 40 years, researchers have discovered a new drug that may help fight tuberculosis.

Currently known as R207910, the drug belongs to a class of compounds called diarylquinolones (DARQs) that work by cutting off the bacteria's energy supply.

"The hope is that it will be effective against drug-resistant tuberculosis and that it will help to shorten treatment regimens from six months downwards to say two months or so," said Christopher Dye, coordinator of Tuberculosis Monitoring and Evaluation for the World Health Organization (WHO).

In the Dec. 9 online issue of Science, European researchers report success in treating tuberculosis with the new drug in mice. And the drug was tolerated well by healthy human volunteers in an early clinical trial.

Tuberculosis is an airborne infectious disease that spreads much like the common cold. It's estimated that one-third of the world's population has already been infected with tuberculosis, according to the WHO. Fortunately, many people are naturally able to keep the infection at bay and only 5 percent to 10 percent of those infected become sick or infectious. Still, more than 2 million deaths were caused by tuberculosis in 2002, according to the WHO.

Compounding the problem, more than 11 million people are also co-infected with the HIV virus, and some tuberculosis medications can't be used in conjunction with HIV medications. Also, some strains of the tuberculosis bacteria have developed resistance to some of the first-line tuberculosis treatments.

Dye said there's a definite need for new medications because current treatments take too long, some have toxic side effects, and some don't work against certain strains of the disease.

The new drug was discovered through a search of the Johnson and Johnson chemical "library" that catalogs compounds the company has developed. R207910 wasn't originally designed as an antibiotic, but as a drug to dampen the immune system.

While the drug was a failure for its original purpose, the researchers saw an unexpected benefit from the compound.

"The chemical reaction [against the tuberculosis bacterium] was an unintentional side effect," explained study author Koen Andries, a research fellow at Johnson and Johnson Pharmaceutical Research and Development in Beerse, Belgium.

Lab tests in culture showed the compound was effective against several different mycobacteria, even against drug-resistant strains of M. tuberculosis. But the drug appears to leave other bacteria unharmed, which is a benefit because it will leave "good" intestinal bacteria intact and won't contribute to the growing problem of drug resistance with other bacteria, the researchers said.

Andries and his colleagues then tested R207910 in mice along with two other commonly used tuberculosis medications, isoniazid (H) and pyrazinamide (Z). The reason these drugs were used in combination was to lessen the likelihood of drug resistance developing. The current drug cocktail used for tuberculosis is referred to as RHZ. The R is for rifampin. The drug cocktail under study is called GHZ, with G standing for R207910, Andries said.

After one month on GHZ, the mice had the same bacterial "load" that would have been expected after two months on RHZ. After two months, lung tissue in the mice was completely free of bacteria. That means it could be possible with the new drug to shorten treatment time by as much as 50 percent, according to the researchers.

"Our combination achieves the same results after one month instead of the standard of care for two months," said Andries. "And it's compatible with HIV treatment combinations."

Andries said the researchers also tested the new compound in humans in an early clinical trial. They tested nine groups of nine people each, and each group got different doses of the medication.

"So far, so good," said Andries. "But it was only for a limited time period, two weeks. We cannot be certain that no side effects can emerge." However, he added, there were no differences in side effects between the treated groups and a placebo group, so the researchers are hopeful the drug will be well-tolerated.

Next, the researcher plan to move on with human trials, though Andries offered no details on how soon the next phase would begin.

Added Dye: "These are exciting results from experiments with mice. The crucial next step is to demonstrate efficacy in human trials."

More information

To learn more about tuberculosis, visit the World Health Organization.

SOURCES: Koen Andries, Ph.D., D.V.M., research fellow, Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium; Christopher Dye, D.Phil., coordinator, tuberculosis monitoring and evaluation, World Health Organization; Dec. 9, 2004, Science online
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