Research: A single-dose drug for Buruli ulcer

By: Amanda Lee, Writer (Communications & Outreach)

Buruli ulcer begins as painless skin nodules that develop into a debilitating, necrotizing infection of the skin and soft tissue if untreated. 

The flesh-eating disease, which is caused by the bacterium Mycobacterium ulcerans, is present in at least 33 countries spanning across Africa, South America, Asia, and the Western Pacific in tropical, subtropical, and temperate areas. Australia and Japan are both classified as endemic areas. 

About 48 per cent of those affected in Africa are children who are below 15 years old.

A potential treatment for Buruli ulcer
While Buruli ulcer can be cured with early detection and a combination of antibiotics, the disease can also lead to permanent disfigurement and disability if diagnosed late. The current treatment of Buruli cancer consists of a combination of antibiotics taken for eight weeks, and often complemented with surgical interventions.

However, there could be a single-dose cure for the disease after an international team of researchers validated the use of an anti-tuberculous drug candidate, Telacebec (Q203), in a mouse model of Buruli ulcer infection.

Telacebec was developed by a team led by LKCMedicine Assistant Dean for Research and Associate Professor of Infectious Disease Kevin Pethe, while working at the Institut Pasteur Korea.

Previously, A/Prof Pethe worked with the Swiss Tropical and Public Health Institute (Swiss TPH) to demonstrate that Mycobacterium ulcerans is exquisitely sensitive to Telacebec.

In a study published in the peer-reviewed journal Nature Communications in 2018, the researchers found that the drug candidate was particularly potent in a mouse model of Buruli ulcer infection. They also discovered that the drug candidate can be given on alternate days at a low dose, something not possible with the current standard of care.

 
Taking his research further, A/Prof Pethe worked with a team of researchers and tested the effectiveness of a single dose of Telacebec in a mouse model of Buruli ulcer.

In a paper published in the journal Antimicrobial Agents and Chemotherapy in August, the researchers established that Telacebec was able to eradicate the disease when given at a single dose, or at four lower weekly doses.

"The resolution of disease symptoms in mice was achieved much faster than the current approved treatment protocol for Buruli cancer. No relapse was observed up to 19 weeks after administering the single dose of Telacebec, suggesting that the treatment is curative," said A/Prof Pethe, who has been spending his career working on drug discovery for multi-drug resistant TB.

The team includes researchers from NTU Institute for Health Technologies, the Indian Institute of Integrative Medicine, the clinical microbiology division of the Indian Institute of Integrative Medicine, and the Swiss Tropical and Public Health Institute.

"Telacebec holds exceptional promise as a drug candidate for the treatment of Buruli ulcer. The concept of a single-dose cure opens the possibility of developing a simplified and safe regimen to treat the disease," said A/Prof Pethe.

Agreeing, first author of the paper Dr Sangeeta Susan Thomas said the exquisite potency of Telacebec against Mycobacterium ulcerans coupled with its ability to linger in the body for a long time makes it an exceptional candidate for a single dose therapy for Buruli ulcer. The drug also bears an excellent safety profile that fits a single drug therapy for Buruli ulcer, she added.

Moving forward, human clinical trials will be necessary to validate the promise of Telacebec or related drugs for the treatment of Buruli ulcer.