Promising New Compound Targets Tuberculosis Bacteria

A recent study published in the journal Nature highlights a promising new compound called CMX410, which targets a crucial enzyme in Mycobacterium tuberculosis, the causative agent of tuberculosis. This compound shows success even against drug-resistant strains, which pose a growing global challenge, making treatment more difficult and less effective.

Research Team and Academic Collaboration

This research was led by Dr. James Sacchettini, a professor at Texas A&M University, in collaboration with Dr. Casey McNamara, Director of Infectious Diseases at the Caliber-Scripps Institute for Innovative Medicines, a division of Scripps Research developing next-generation therapies.

The discovery emerged from collaboration within the Tuberculosis Drug Accelerator Program, an initiative funded by the Bill and Melinda Gates Foundation that brings researchers together to advance promising tuberculosis treatments.

A New Approach to an Old Enemy

The new compound identified by AgriLife Research and the Caliber-Scripps Institute disrupts a crucial enzyme called Pks13, which the bacteria need to build their protective cell wall. Without this structure, Mycobacterium tuberculosis cannot survive or infect the body.

Scientists have long known that Pks13 is an important target for tuberculosis drugs, but developing a safe and effective inhibitor has proven challenging. CMX410 succeeds where previous attempts failed, featuring a design that makes it highly specific to its target, thus reducing unwanted side effects.

Chemical Technique and Its Use in Drug Design

To achieve this breakthrough, researchers used a technique known as click chemistry, a method that links molecules together like puzzle pieces. This approach was developed by Professor Barry Sharpless, a Nobel laureate in chemistry at Scripps.

McNamara stated, “This method represents a new tool in drug design. We expect its applications to expand in the coming years to help address pressing public health issues, including tuberculosis.”

Promising Early Results

The team began by screening a collection of compounds from Sharpless’s lab to find those capable of slowing the growth of Mycobacterium tuberculosis. After months of optimization, CMX410 emerged as the best candidate in terms of efficacy and balance.

The teams tested over 300 variants to adjust the compound’s potency, safety, and selectivity. The final version was tested against 66 different strains of tuberculosis, including multi-drug-resistant samples from patients, and proved effective in nearly all cases.

Conclusion

While further studies are needed before the compound can be tested in humans, the initial results indicate strong potential for future tuberculosis treatment. Dr. Ina Krieger from Sacchettini’s lab said, “We are working to discover new drugs that disrupt essential biological processes and determine optimal concentrations with current medications to enable shorter, safer, and more effective treatment regimens.”