Using an innovative approach that bypasses traditional antibiotics,UBC researchers have discovered a 70-year-old Parkinson’s drug is a strong candidate for treating tuberculosis (TB).
Caused by the bacteria Mycobacterium tuberculosis (Mtb), TB has persisted for centuries and still remains one of the deadliest infectious diseases worldwide. Its resilience stems from its unique biological features, including a waxy, impermeable cell wall, a slow growth rate, and the ability to enter a dormant state that allows it to evade drugs and the immune system.
The current standard treatment is challenging: up to four antibiotics taken daily over several months. Barriers such as poverty can make accessing treatment more difficult.
“There is an adherence issue due to the complexity of treatment and the side-effects. [Patients] discontinue it, and this leads to resistance,” said Dr. Henok A. Sahile, lead author and post-doctoral researcher in the Faculty of Medicine. ”It’s a vicious cycle.”
This investigation emerged during the COVID-19 pandemic, as the research team screened over FDA-approved drugs, compiled by Medicines for Malaria Venture (MMV). The MMV library contained drugs that were thought to be useful against COVID-19, and because SARS-CoV-2 has some similarities to TB pathogens, the research team thought the drugs could be used to fight TB as well.
The compounds were tested on human macrophage (immune cell) models infected with Mtb. Benztropine, a drug used for regulating muscle control and stiffness in Parkinson’s disease, , emerged as a promising candidate.
“[Benztropine] activates human cells … so they are capable of killing the [bacteria] by themselves,” said Sahile.
Unlike standard TB antibiotics, which directly target the bacteria, this drug uses a host-directed approach. It activates host macrophages to fight the infection instead of directly killing the bacteria.
“It could shorten the treatment duration [and] reduce the emergence of drug resistance.”
Using fluorescently tagged Mtb in macrophages, the team compared the drug's effectiveness to standard antibiotics. While it inhibited roughly 70 per cent of bacterial growth, the drug’s mechanism still gives it a unique advantage over conventional treatments.
Drug repurposing is a method that uses existing drugs for new treatment purposes. This method leverages medications with known safety profiles and reduces the cost and time needed compared to creating new drugs from scratch. This technique to repurpose drugs is not new; relatively recently, many antivirals were repurposed from existing drugs during the COVID-19 pandemic.
Sahile and his team are now exploring combinations of repurposed drugs with existing TB antibiotics to shorten treatment duration and combat bacterial resistance. They are also screening alternative compounds with similar host-activating properties but fewer side-effects than Benztropine, with future plans for animal studies and, eventually, clinical trials.
He explained that because the drug targets human cells rather than Mtb, it can be applied to other bacteria as well.
“We’re trying to refine this work with different pathogens [and under] different conditions,” said Sahile.
