Innovative Engineered Drug Targets Mycobacterium abscessus, A Dangerous NTM Similar to Tuberculosis

Researchers from the Hackensack Meridian Center for Discovery and Innovation (CDI) have announced a significant breakthrough in the fight against Mycobacterium abscessus, a highly resistant and rapidly growing nontuberculous mycobacterium (NTM) that poses a severe threat to immunocompromised individuals and those with lung diseases. In a recent study published in Proceedings of the National Academy of Sciences, scientists detailed the development of a new drug candidate engineered to target this stubborn pathogen.

Mycobacterium abscessus is known for its resistance to traditional antibiotic treatments, particularly the rifamycin class of antibiotics developed in the 1960s, which are effective against tuberculosis but often fail against this NTM. This resistance complicates treatment options, especially for cystic fibrosis patients, who are increasingly at risk. Moreover, the widespread use of rifamycin antibiotics has been limited by issues such as drug interactions and limited efficacy.

To overcome these challenges, the research team conducted an extensive medicinal chemistry effort, re-engineering existing rifamycin antibiotics to enhance their activity and pharmacokinetics. Over five years, they designed and tested numerous analogs, focusing on overcoming drug resistance, ensuring potency, and improving oral absorption, while also reducing adverse drug interactions.

Two standout compounds demonstrated exceptional effectiveness in laboratory models, showing promise not only against M. abscessus but also other rapidly growing mycobacteria such as Mycobacterium avium complex (MAC) and Mycobacterium tuberculosis. These second-generation rifamycins could mark a breakthrough in treating difficult mycobacterial infections.

The urgency of this development is underscored by the rising prevalence of M. abscessus infections, especially among cystic fibrosis patients. Environmental studies suggest that exposure to certain minerals and metals in water supplies may increase infection risk. The initial discovery was led by Dr. Uday Ganapathy at the National University of Singapore, with ongoing advancements driven by collaborations across academia and health institutions worldwide.

According to Dr. Thomas Dick, one of the lead researchers, this interdisciplinary effort involved contributions from medicinal chemists, microbiologists, and clinicians, with notable work from Dr. Courtney Aldrich and Dr. Mercedes Gonzales-Juarrero. The team aims to advance these drug candidates into clinical trials, potentially providing a new, effective treatment for resistant mycobacterial infections.

This breakthrough represents a promising step towards addressing a significant unmet medical need, and could lead to the development of a new class of antibiotics with broader applications in infectious disease treatment.