A Faster TB Treatment?
Taking a new approach toward tuberculosis therapy, a UCLA-led research team has devised a potential drug regimen that could cut the treatment time by up to 75 percent, while simultaneously reducing the risk that patients could develop drug-resistant TB.
To identify the regimen, the researchers launched a systematic search for an optimal drug treatment using the Parabolic Response Surface Platform, a data analysis method that identifies which drug combinations work synergistically — that is, with individual drugs working together in a way that is more potent than the sum of their individual potencies.
The study, published in the peer-reviewed journal Nature Communications, is the first to use the platform to identify more effective TB drug regimens and one of the first to focus on a communicable disease.
TB is one of the world’s deadliest diseases, killing more people than any other disease caused by a single infectious organism. Worldwide, about 10 million people develop active TB each year and about 1.5 million people die of the disease, with India, Indonesia, China, Nigeria, Pakistan and South Africa accounting for 60 percent of the total, according to the World Health Organization. The United States saw 9,557 cases in 2015 and, according to the most recent data available, 493 deaths from the disease in 2014. More than 2 billion people have latent infections of the disease-causing bacterium, Mycobacterium tuberculosis, meaning they could ultimately develop active disease.
The current standard for treating TB is a four-drug regimen that has been in use since the 1980s. It was developed through trial and error, with physicians adding or substituting one drug at a time to existing regimens, rather than through a systematic search for synergistic drugs.
The regimen is unusually onerous, requiring six to eight months of therapy, said Dr. Marcus Horwitz, Distinguished Professor of Medicine and Microbiology, Immunology & Molecular Genetics at the David Geffen School of Medicine at UCLA and the study’s senior author.
“The lengthy course increases the likelihood of drug toxicity and often leads to poor patient adherence to the drug regimens, which in turn prompts the emergence of drug-resistant TB,” he said. “Drug-resistant TB, which requires up to two years to treat with current regimens, is difficult to treat and carries a high fatality rate.”
The PRS technology can be applied to any disease and has been used in oncology, infectious diseases, immunosuppression and other areas in both the lab and the clinic, said Chih-Ming Ho, Distinguished Research Professor of Mechanical and Aerospace Engineering at the UCLA Henry Samueli School of Engineering and Applied Science, and principal investigator of this study.