Cancer medicine unlocks the softer death for TB Culprit

A medication for cancer treatment currently in clinical trials could strengthen tuberculosis therapy by triggering a more controlled cell death process, which potentially reduces pulmonary damage in survivors, according to medicine researchers Johns Hopkins.

The Navitoclax experimental medicine, when added to standard tuberculosis (TB) treatments, helped infected cells through a controlled process called apoptosis instead of the most harmful necrosis that generally occurs in TB infections, found the study.

“The current TB treatment regimes are long, expensive and leave patients vulnerable to relapse and pulmonary scars. Our research shows that adding a therapy led by the host Pediatrics at the University of Johns Hopkins University of the University of Medicine of Hopkins.

The findings, published in the March 27 edition of Nature communicationsIt could lead to more effective treatments that reduce the severity of lung disease after TB, a condition that affects dozens of millions of TB survivors worldwide.

Despite being preventable and treatable, tuberculosis has probably recovered its position as the most fatal infectious disease in the world, causing approximately 1.25 million deaths and 10.8 million new cases in 2023, according to the World Health Organization. Hundreds of thousands of these infections resist standard antibiotics.

When Mycobacterium tuberculosis, the bacteria responsible for TB, infects lung cells, manipulates cell death paths in their favor. In the early stages of infection, infected cells normally suffer apoptosis, a regulated and less harmful form of cell death. However, as infections advance, bacteria trigger necrosis, an uncontrolled cell death that causes inflammation and damage to the surrounding tissues.

“While apoptosis could be compared to the controlled demolition of a building,” Jain explained, “necrosis is more like the destruction of a pump.”

TB bacteria achieve this by inciting infected cells to produce BCL-2, a family of antiapopptototic proteins. “This kidnapping of a typically healthy molecular route has significant advantages for M. tuberculosis,” said Medha Singh, the first author of the study and member of pediatric infectious diseases in the Faculty of Medicine. Create “necrotic niches within the lung that avoid the attacks of the immune system and allow bacteria to multiply.”

To test whether inhibit BCL-2 could improve the results of TB treatment, researchers treated mice infected with M. tuberculosis using standard TB antibiotics: rifampina, isoniazide and pyrazinamide. Some mice also received Navitoclax, a BCL-2 inhibitor currently in cancer clinical trials.

After four weeks, the mice that received standard and Navitoclax antibiotics showed notable improvements compared to those of the antibiotics alone. They had 40% less necrotic pulmonary lesions, and the infection was less likely to spread to other organs such as the spleen. Combined treatment also reduced pulmonary scars by 40%.

Image studies that use positron emission tomography (PET) showed that the addition of Navitoclax doubled the amount of pulmonary apoptosis. Although Navitoclax had no direct effect on M. Tuberculosis when used alone, animals that receive the medication together with antibiotics decreased their bacterial load 16 times more effectively than those that received only standard treatment.

These results suggest that Navitoclax could offer similar benefits for patients with TB and those with other chronic bacterial infections prevalent in the US.