TUBERCULOSIS: Towards a first non-antibiotic drug treatment

Towards a first non-antibiotic drug treatment

With nearly 10 million cases worldwide and 1.7 million deaths, tuberculosis (TB) remains the second leading cause of death linked to a single infectious agent. Multi-resistance of Mycobacterium tuberculosis (MR-TB) to antibiotics is also known. After 50 years of no development of new anti-tuberculosis drugs, these scientists have developed the first non-antibiotic drug capable of effectively treating tuberculosis, at this stage in animals. The researchers, who publish their work in the Journal of Medicinal Chemistry, hope to be able to move into clinical trials within 3 to 4 years.

For more than 60 years, the only drugs doctors have had available to fight TB are antibiotics. But resistance is becoming an increasingly serious problem and prolonged treatment is difficult and painful for patients: they are forced to take a cocktail of powerful antibiotics for 6 to 8 months, with frequent side effects and a risk 20% resurgence. 10 years of painstaking research have enabled the development of this candidate which targets the defenses of Mycobacterium tuberculosis rather than the bacteria itself and, in this way, can eliminate its most antibiotic-resistant strains.

 

The candidate reduces the bacterial load in animals: 

the team from the University of Manchester (UK) and Rutgers University (US) is testing the drug here in guinea pigs with acute and chronic tuberculosis infection. And the compound, which does not kill bacteria directly, results in a remarkable reduction in bacterial load, explains lead author Prof. Lydia Tabernero: “  With current treatments, there is no guarantee that the disease will be eliminated: antibiotics do not do not eliminate the infection and the risk of becoming infected with drug-resistant bacteria remains very high. But by deactivating the defenses of these bacteria, we have the opportunity to improve the efficiency of the immune system and thus eliminate the pathogen  ”.

 

Mycobacterium tuberculosis secretes virulence factors

the cell's secret weapon that blocks the immune response to infection. However, a virulence factor called MptpB proves to be an appropriate target here because, when it is blocked, the white blood cells can “do their job” and more effectively eliminate Mycobacterium Tuberculosis. In addition, blocking MptpB does not cause any toxicity for human cells. Finally, since the bacterium is not directly threatened, it is less likely that it will develop resistance against this new agent.

 

According to the authors, they have a significant step forward, the next step of which will be to optimize the compound in order to be able to conduct the first clinical trials within 3 to 4 years.