A medication developed in the 1950s to treat Parkinson's disease may offer a powerful new tool in the fight against tuberculosis (TB), according to new research from the University of British Columbia.
Published in npj Antimicrobials & Resistance , the study found that benztropine, a drug used to manage tremors in patients with Parkinson's, can dramatically reduce levels of TB-causing bacteria by boosting the body's natural immune response.
TB is the world's deadliest infectious disease, typically affecting the lungs and causing an estimated 1.3 million deaths each year. Treatment requires a months-long regimen of multiple antibiotics, which can have serious side effects and is increasingly challenged by the emergence of drug-resistant bacterial strains.
"New approaches for treating tuberculosis are urgently needed," said senior author Dr. Yossef Av-Gay , a professor of infectious diseases at the UBC faculty of medicine. "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."
Tuberculosis is particularly difficult to treat because the bacteria responsible, Mycobacterium tuberculosis, is able to infect and survive within the very immune cells designed to destroy pathogens, known as macrophages.
While antibiotics work by killing the bacteria directly, benztropine functions through an alternative approach that supercharges immune cells to fight back. The drug blocks a receptor on macrophages that TB bacteria exploit, allowing the cells to regain their ability to kill the bacterial invaders.
The researchers say treatments that enhance the body's natural defences, known as host-directed therapies, could offer significant benefits in the fight against TB.
"Because these therapies don't directly target the bacteria, they're far less likely to drive drug resistance," said lead author Dr. Henok Sahile , a postdoctoral researcher in UBC's faculty of medicine. "They can also work in combination with existing antibiotics to improve treatment outcomes or help in cases where antibiotics fail."
To identify benztropine, the research team screened a library of more than 240 U.S. Food and Drug Administration-approved drugs by testing each compound on immune cells infected with TB.
Benztropine emerged as a standout candidate, capable of significantly reducing TB bacterial counts in experiments with both human and mouse immune cells. The researchers then tested benztropine in mice infected with TB, with oral treatment leading to a 70 per cent reduction in bacterial load in the lungs—comparable to some current TB treatments.
The drug showed similar effectiveness in a separate mouse model of Salmonella infection, suggesting its potential as a treatment for a wide range of pathogens.
Because benztropine is already approved for use in humans, the researchers say the findings could accelerate its path to clinical testing for TB and other infections.
"Repurposing existing drugs is one of the fastest and most cost-effective ways to bring new treatments to patients," said Dr. Av-Gay. "With benztropine, we already understand the safety profile and pharmacology, which means we can move more quickly toward clinical trials."
The interdisciplinary research team involved microbiologists, immunologists and infectious disease experts at UBC's Life Sciences Institute, as well as collaborators at the Vaccine and Infectious Disease Organization at the University of Saskatchewan.
This study was supported by the Canadian Institutes of Health Research.
Interview language(s): English, Hebrew (Av-Gay), Amharic (Sahile)
