AsianScientist (Apr. 5, 2016) – Researchers from China and the US have made an important step toward a substantially faster and more effective treatment for tuberculosis, which infects some ten million people and causes 1.5 million deaths each year. They have developed combination drug treatments that kill tuberculosis-causing bacteria much faster than the current standard treatment. Their research was published in the Proceedings of the National Academy of Sciences.
Combination therapy, which uses a series of drugs, is the clinical standard for many major diseases. However, the number of potential combinations of different drugs and dose levels can be in the billions, making the prospect of choosing the best one seem daunting.
In the study, researchers from Shanghai Jiao Tong University and University of California Los Angeles used a technique called feedback system control to study cells infected with the bacteria that cause tuberculosis. They quickly narrowed combinations of 14 different tuberculosis drugs with five different doses—resulting in six billion possibilities—into several promising combinations.
Current drug therapies for drug-sensitive tuberculosis require six to eight months of treatment; for drug-resistant tuberculosis, treatment can take as long as two years. The standard treatment regimen for drug-sensitive tuberculosis comprises four different drugs. Many patients stop taking the drugs before completing treatment, enabling the emergence of drug-resistant tuberculosis strains.
The researchers infected macrophages, a type of human white blood cell, with a highly virulent strain of tuberculosis. The bacteria were engineered to fluoresce while they lived, so drug regimens that eliminated the fluorescence killed the bacteria.
Feedback system control quickly eliminates potential dead ends and automatically readjusts drug-dose combinations to zero in on the most effective ones, saving a tremendous amount of time and effort. This allowed the researchers to identify ideal drug-dose combinations after just four rounds of testing, with about 125 tests per round.
“Designing a drug combination with optimized drug-dose ratios has, until now, been virtually impossible,” said Dr. Ho Chih-Ming, the study’s principal investigator.
“Feedback system control technology demonstrated it can pinpoint these best possible ratios for a wide spectrum of diseases.”
The research team also found that two major tuberculosis drugs, isoniazid and rifampin, were counterproductive when combined with other drugs. Another drug, clofazimine, which is not usually used in tuberculosis treatments, was included in most of the promising combinations.
The researchers have also completed an unpublished animal study, the results of which have prompted human trials of one promising combination. Plans are also underway to test another.
“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,” said senor author Dr. Marcus Horwitz.
“This will increase the likelihood of successful treatment and decrease the likelihood of patients developing drug-resistant tuberculosis.”
The article can be found at: Silva et al. (2016) Output-driven Feedback System Control Platform Optimizes Combinatorial Therapy of Tuberculosis Using a Macrophage Cell Culture Model.
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Source: University of California Los Angeles; Photo: Shutterstock.
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