Novel combination therapies could greatly improve treatment of tuberculosis

Researchers from the University of California, Los Angeles (CA, USA) and Shanghai Jiao Tong University (Shanghai, China) have utilized a novel technique to study the potential of different drug combinations as faster and more effective treatment options for tuberculosis.

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Tuberculosis infects around 10 million people every year, and causes 1.5 million deaths, yet treatment options are expensive, time-consuming and often ineffective. However, a team of researchers from the University of California, Los Angeles (CA, USA) and Shanghai Jiao Tong University (Shanghai, China) have utilized a technique called feedback system control, developed at the University of California, Los Angeles, to study the impact of different combinations of tuberculosis drugs, producing several promising combination treatments that could be much more quickly effective than standard regimens.

Combination therapy, which consists of a series of drugs, is used to treat many major diseases, but there can potentially be billions of potential combinations of drugs and dosages, making testing for the most effective option a complex task. The researchers addressed this by employing feedback system control to study cells infected with tuberculosis-causing bacteria, quickly narrowing a field of over 6 billion possible combinations of 14 different drugs and five doses to several promising combination treatments capable of killing the bacteria much faster than the current standard regimen for tuberculosis.

“Designing a drug combination with optimized drug-dose ratios has, until now, been virtually impossible,” explained the study’s principal investigator, Chih-Ming Ho. “Feedback system control technology demonstrated it can pinpoint these best possible ratios for a wide spectrum of diseases.”

“If our findings are confirmed in human studies, the new drug regimens that we have identified should dramatically shorten the time needed to treat tuberculosis,” added Marcus Horwitz, a senior author of the research. “This will increase the likelihood of successful treatment and decrease the likelihood of patients developing drug-resistant tuberculosis. A highly successful and rapid treatment may hasten the eventual eradication of tuberculosis.”

Currently available therapies for drug-resistant tuberculosis take up to 2 years to complete, with drug-sensitive tuberculosis taking 6–8 months. The standard regimen for the latter is a combination of four different drugs, and many patients stop taking the drugs before completing the treatment, enabling drug-resistant strains to emerge.

Feedback system control quickly eliminates dead ends and quickly adapts to effective drug-dose combinations, saving researchers time and effort and allowing them to identify ideal drug-dose combinations after only four rounds of testing. The team also completed an animal study, prompting human trials of one of the identified combinations, with plans underway to test another.


Silva A, Lee B-Y, Clemens DL et al. Output-driven feedback system control platform optimizes combinatorial therapy of tuberculosis using a macrophage cell culture model. PNAS doi: 10.1073/pnas.1600812113 (2016) (ePub ahead of print);

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Stella Bennett

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