New consortium receives NIH grant to accelerate development of effective TB treatments

A new consortium co-led by Weill Cornell Medicine, has been awarded a five-year, $31 million grant from the National Institutes of Health's National Institute of Allergy and Infectious Diseases to accelerate the development of faster, more effective treatment regimens for tuberculosis (TB). Investigators at the University of California, San Francisco; Johns Hopkins Medicine; and Vanderbilt University Medical Center comprise the other co-leads.

The Preclinical Design and Clinical Translation of TB Regimens (PreDiCTR) consortium brings together more than 30 multidisciplinary investigators from 20 institutions in 6 countries. They aim to identify the most promising new and existing treatment combinations for the disease and help advance them toward clinical trials.

One of the key goals is to reduce the time patients spend in therapy to be cured of TB. Some progress has been made shortening the even longer regimens needed to treat drug resistant strains, but faster regimens for drug-sensitive strains of the disease are desperately needed."

Dr. Dirk Schnappinger, professor of microbiology and immunology at Weill Cornell Medicine and one of the study's four co-principal investigators

Worldwide about 10 million people develop TB and about 1. 5 million die each year from the disease, according to the World Health Organization. Despite the availability of curative antimicrobial therapies, disease control and eradication has proved elusive.

A lack of new drug development and long and arduous existing treatment regimens have contributed to a lack of progress. Dr. Schnappinger explained that current therapies start with an intense phase of four drugs followed by two drugs-;a process that can last for six months in total and often requires supervised drug administration. However, patients may stop therapy early, which can lead to relapsing symptoms, disease spread and the emergence of new hard-to-treat drug-resistant strains.

"Symptoms improve relatively quickly, and there is a temptation not to continue therapy as directed," he said. Limited resources in the lower-income countries where TB is most prevalent may compound these challenges. 

The consortium brings together experts with complementary expertise in molecular genetics, computational biology, preclinical studies, and clinical trials to prioritize the most promising combinations of new and existing drugs for clinical trials.

The consortium's other co-principal investigators are Dr. Rada Savic of the University of California, San Francisco; Dr. Kelly Dooley of Vanderbilt University; and Dr. Eric Nuermberger of Johns Hopkins University. Dr. Schnappinger will work with other Weill Cornell investigators to identify the molecular mechanisms that make some TB drug combinations more effective than others, using data from clinical trials and working backward.

The team plans to collaborate with other ongoing TB consortia and drug companies that make existing TB drugs or are developing new ones.

"We are hoping to close a gap in TB research," Dr. Schnappinger said. "We are focused on translational studies that advance the results of preclinical research into clinical trials and use insights from clinical trials to further refine TB therapies."

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