New TB approach heralds new treatment
effective against tuberculosis (TB), a disease that has made a
comeback due to the emergence of resistant strains of the offending
bacterium and the spread of AIDS.
This latest discovery adds to the current battle being waged upon a growing list of diseases, which have become resurgent, often in a stronger more drug resistant form.
Antibiotic-resistant strains of TB have made current treatments less effective. In addition, the HIV-AIDS epidemic sweeping across many parts of the world is making matters worse since the killer disease often triggers the latent TB which is carried by an estimated one in three of the world's population.
The team at Johnson & Johnson's research centre in Belgium have been testing the compound R207910, which belong to a new family of anti-TB agents called diarylquinolines (DARQ).
"The drug acts through a novel mechanism of action, and is therefore active against multi-drug resistant (MDR) strains of TB tested so far," Dr Koen Andries, lead researcher at Johnson & Johnson pharmaceutical research and development commented.
R207910's mechanism of action is unique in the way it works. The compound attacks an enzyme called ATP synthase, the energy source for the bacterium. Animal studies showed this new compound enters the bloodstream and concentrates in lung cells, which harbour the TB bacilli, killing the bacilli soon after they enter the body. R207910 lingers in the body for days continuing to kill bacilli even when administered only once a week in mice.
Currently in human trials, the drug appears to have better antibiotic properties than the drugs currently in use, a feature that it could drastically speed up treatment time.
TB is currently treated with a cocktail of drugs which must be taken for six to nine months, prematurely ending treatment is one reason why resistant strains emerge. Results suggest that R207910 can cure it in about half the time.
The resurgence of TB has prompted the World Health Organisation (WHO) to declare a global health crisis. With 2 million deaths worldwide every year, mainly in third world countries, an effective yet cost-effective treatment would prove potentially lucrative for its producers.
No new anti-TB drugs have been brought into the clinic in the past 40 years, and although doctors have effective first-line TB drugs that work, there have been difficulties getting these medicines to the patients who need them as well as effectively treating patients with drug resistant disease.
A potential treatment strategy involving R207910 and a current TB drug looks likely. A combination excluding Rifampin (Systemic), the current choice of treatment, would be compatible with anti-HIV drugs, making it suitable for treating patients co-infected with HIV and TB.
However, Andries added, considerable work needs to be done to fully determine this compound's clinical potential. Since the compound seems to be safe and well tolerated in Phase I studies with healthy human volunteers, R207910 will now be tested in humans with active pulmonary TB.
One out of three people in the world are infected with latent TB. Even in the developed world, one out of 20 carry the TB bacillus. In some developing countries, one in two people are infected. A carrier of latent TB has a 10 per cent life-long risk to develop TB. However, in HIV patients, that risk is 10 per cent per year.
