A novel antibiotic that is working well in mice may be the first new drug enlisted in the fight against tuberculosis in 40 years, an international team of researchers said on Thursday.

It works in a new way to shut down the bacteria that cause tuberculosis, said Dr. Koen Andries of the U.S. drug and household products giant Johnson & Johnson, who led the study.

“This drug is apparently cutting off the energy supply of the bacteria,” Andries said in a telephone briefing.

It might be added to the cocktails used for tuberculosis to speed up the treatment, which takes months, the researchers report in this week’s issue of the journal Science.

Experts hope it can cut down on the treatment time needed, helping patients to achieve a real cure and helping to stop the TB bug from mutating into forms that resist drug treatment.

Originally developed as an immune system drug, the new drug was a failure and languished in the drug library of Johnson & Johnson before being rediscovered, Andries said.

The drug, known only by its experimental name R207910, has been tested in people in a Phase I safety trial and seems to cause no serious side effects. The company is proceeding to Phase II, the second of the three phases of experiments needed before seeking U.S. Food and Drug Administration approval.

The drug is in a new class called diarylquinolines.

It works by shutting down the bacteria’s source of power, an enzyme called ATP synthase.

World Health Organization tuberculosis expert Dr. Christopher Dye called the finding a breakthrough.

“WHO’s role in future clinical trials is not yet clear,” Dye added in an interview conducted by e-mail.

Globally, one out of three people are infected with latent tuberculosis, which is easily transmitted even without symptoms. There are up to 10 million new cases of active TB each year and 2 million people die of it annually.

TB has made a comeback in many parts of the world because of the AIDS virus epidemic. HIV infection makes people more susceptible to the tuberculosis bacillus.

LENGTHY TREATMENT

TB is treated with a cocktail of antibiotics, including rifampin, isoniazid, and pyrazinamide, which must be taken for six to nine months.

But the bacteria are becoming resistant to drugs and there are now strains that resist several of the antibiotics used against it.

So anything new to add to the arsenal is welcome, even though the researchers note that TB will eventually develop resistance to the new drug, too.

“Given the high rates of drug-resistant TB that we are seeing, especially in former Soviet countries, it is hugely worrying that no new anti-TB drug has been discovered for over 30 years,” Dye said.

“The neglect in TB drug development is due partly to the fact that TB was thought, in the western world, to be a disease of the past. Investment in drug discovery has also been low because the market is in the poorest parts of the world - customers (TB patients) are mostly poor people who cannot afford to pay for costly treatments developed by major drug companies. “

Andries said his team, which included scientists across Europe, had been actively seeking a new antibiotic to try against TB. They used a common method of screening drug libraries, which are collections of chemical formulas for various drugs that companies keep in their records.

They happened upon a promising drug that was originally synthesized to attack interleukins - immune system chemicals involved in inflammation. The drug did not work as expected and was shelved, but its formula was saved “just in case,” Andries said.

SOURCE: Science, December 10, 2004.