New Weapon to Fight Tuberculosis

New Weapon to Fight Tuberculosis

BTZ043 is a new therapeutic agent to fight tuberculosis. Its target is an enzyme which produces the cell wall of the pathogenic bacterium Mycobacterium tuberculosis. This research could lead to a much-awaited new TB drug.

According to the World Health Organization (WHO), each year tuberculosis affects another 5.4 million people (including relapses) and continues to kill almost two million individuals across the globe. Most new cases occur in Asia or Africa. In Europe, the epidemic was slowed down by antibiotics in the 1950s-1970s but is again gaining ground due to the emergence of multidrug-resistant strains which contaminate 490,000 people each year, mainly in countries of the former Soviet Union.  Contamination by this infectious disease is extremely effective as it goes through the respiratory system. There is therefore an urgent need for new TB drugs. 

The team led by Professor Cole, Head of the EPFL Global Health Institute, has been researching new therapies to cure TB for three years in the framework of a European project entitled NM4TB. Their research has had spectacular results as it has led to the development of a chemical compound which proved effective against the bacterium without side-effects in mice, as brought to light in the article published today by “Science” magazine.

Vadim Makarov, of the Bach Institute of Biochemistry of the Russian Academy of Sciences in Moscow, the main author of the article published in “Science”, indicates that the researchers started by synthesizing a series of sulfur-containing compounds, which were then tested for antibacterial and antifungal activity. Research subsequently focused on a specific group: benzothiazinones, one of which – BTZ043 – proved particularly effective against the tubercle bacillus. The latter’s cell walls, with their particular wax-rich structure, confer high resistance to antiseptics, some antibiotics and macrophages.

The new compound inhibits the enzyme which produces the molecule linking the various layers of the bacterial cell wall. “Without this enzyme, the bacterium explodes”, the Professor notes. Identifying this target was in itself the major discovery in this research as it paves the way for further therapeutic prospects. The research also relied on many advanced technologies developed by the EPFL. BTZ043 is now exiting preclinical research, soon to be the subject of clinical testing in humans. A new therapy could emerge in under 10 years.

For further information:  Stewart Cole, 021/693’18’51, e-mail:  stewart.cole at epfl ch



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