Scientists have announced a breakthrough that could lead to new treatments for drug-resistant tuberculosis (TB), one of the world’s deadliest infectious diseases.
Researchers from Imperial College London and the London School of Hygiene & Tropical Medicine (LSHTM), working with Johnson & Johnson Innovative Medicine, have identified a crucial vulnerability in the bacteria that causes TB, Mycobacterium tuberculosis. Their findings are published in the journal Nature.
TB remains a major global killer, responsible for over 1.25 million deaths in 2023. Treatment is challenging, requiring patients to take multiple antibiotics for a long time. The difficult side effects often mean people don’t finish their course, which has led to the rise of dangerous drug-resistant strains.
“TB is still a major global problem, to make progress, we need a new and radical approach.” said Dr. Gerald Larrouy-Maumus from Imperial’s Department of Life Sciences, a study co-author.
The team has potentially found just that. By screening thousands of compounds, they discovered a molecule, JNJ-6640, that potently stops the TB bacteria from replicating. They found it works by inhibiting a bacterial enzyme called PurF.
The bacteria need PurF to produce purines—essential molecules for their metabolism and survival. While some germs can steal purines from their human host, the researchers proved that M. tuberculosis cannot. This makes the PurF enzyme an “Achilles’ heel.” When the team blocked it with JNJ-6640 in animal trials, the TB infection was significantly reduced.
While JNJ-6640 itself isn’t stable enough to become a pill, the discovery of this new drug target is what matters most. It opens up an entirely new strategy for developing medications that can overcome existing drug resistance by attacking the bacteria from a different angle.
“There were a lot of hits but one we were quite excited about, we found one that’s incredibly potent against TB.” said co-author Dr. William Pearson at LSHTM.
Efforts are now ongoing to develop new drug candidates that can safely and effectively target PurF, offering new hope in the global fight against TB.
Source: Imperial
