Revived 1950s Parkinson’s drug shows surprising potential against Tuberculosis

A drug first developed in the 1950s for Parkinson’s disease may be an unexpected ally in the global fight against tuberculosis, according to new research from the University of British Columbia (UBC).

Scientists there discovered that benztropine, long prescribed to manage tremors, can help the body’s immune system wipe out tuberculosis-causing bacteria — a breakthrough that could reshape how we approach one of the world’s deadliest infectious diseases.

Tuberculosis, or TB, claims an estimated 1.3 million lives each year, most often by attacking the lungs. Current treatment demands months of multiple antibiotics, which can have harsh side effects and are becoming less effective as drug-resistant strains spread. This is where benztropine’s unique approach stands out. Instead of directly targeting the bacteria like antibiotics do, it boosts the body’s own immune cells, giving them the upper hand.

The bacteria behind TB, Mycobacterium tuberculosis, are notorious for hiding out inside macrophages — the very immune cells meant to destroy invaders. Benztropine works by blocking a receptor on these macrophages that the bacteria use to survive inside the cells. Once that receptor is shut down, the macrophages regain their killing power, wiping out the infection from within.

Senior author Dr. Yossef Av-Gay, a professor of infectious diseases at UBC, said the approach could be a game-changer for tackling drug-resistant TB. “By enhancing immune function rather than targeting the bacteria, this could be a powerful tool against drug-resistant TB. And, it’s a compound that has already proven safe in people with Parkinson’s.”

Lead author Dr. Henok Sahile, a postdoctoral researcher at UBC, added that host-directed therapies — treatments that strengthen the body’s natural defenses — are much less likely to drive resistance. “They can also be paired with existing antibiotics to improve results or help when antibiotics fail,” he said.

The journey to this discovery began with a high-content screening of more than 240 FDA-approved drugs, each tested on immune cells infected with TB. Benztropine quickly rose to the top, showing a remarkable ability to slash bacterial levels in both human and mouse cells.

The team then moved to animal studies, infecting mice with TB and treating them with oral benztropine. The results were striking: a 70 percent reduction in bacterial load in the lungs, comparable to some current TB treatments. Even more intriguing, the drug worked against Salmonella in a separate mouse model, hinting at potential for broader antibacterial use.

Because benztropine is already approved for human use, researchers can skip some of the earliest safety trials. “Repurposing existing drugs is one of the fastest and most cost-effective ways to bring new treatments to patients,” said Dr. Av-Gay. “We already understand its safety and how it behaves in the body, which means we can move faster toward clinical testing.”

The study involved a multidisciplinary team at UBC’s Life Sciences Institute, along with collaborators from the University of Saskatchewan’s Vaccine and Infectious Disease Organization. Their combined expertise in microbiology, immunology, and infectious diseases was key to the discovery.

Over the years, scientists have explored host-directed therapies as a promising alternative to traditional antibiotics for TB. These treatments work by strengthening the body’s immune response, often targeting immune pathways that bacteria manipulate to survive. TB’s ability to persist inside macrophages has made it a prime target for such strategies.

Several repurposed drugs have shown early promise in preclinical models, though none have yet received approval for TB treatment. Past research has also highlighted overlaps in immune responses between TB and other diseases, including COVID-19. Both can trigger harmful inflammation and oxidative stress through similar immune cell pathways, suggesting possible shared drug targets. This has led to cross-disease drug screening, such as testing COVID-19 therapeutics for TB potential.

Despite these advances, translating preclinical findings into successful human treatments has been a major hurdle. Some therapies that worked well in the lab have failed to deliver in clinical trials, reinforcing the need for continued innovation and testing.

If benztropine’s TB-fighting ability holds up in clinical trials, it could give doctors a much-needed weapon against antibiotic-resistant strains. It may also help shorten treatment times, reduce the toxic side effects of prolonged antibiotic use, and improve patient recovery rates.

Beyond TB, the drug’s success against Salmonella hints at potential for tackling other dangerous bacterial infections, especially those that hide inside immune cells. This opens the door to a new class of treatments that focus less on killing bacteria outright and more on empowering the immune system to do its job.

The broader public health impact could be enormous, particularly in regions where drug-resistant TB is spreading fast and healthcare resources are limited. Faster treatment development from drug repurposing could save years of research and millions of lives.

Research findings are available online in the journal npj Antimicrobials and Resistance.

Note: The article above provided above by The Brighter Side of News.

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