The hollow fiber system model of TB was developed about 12 years ago by Tawanda Gumbo, MD, investigator at Baylor Research Institute (BRI) and the director of the Center for Infectious Diseases Research and Experimental Therapeutics at Baylor Institute for Immunology Research (BIIR).
Since the discovery of mycobacterium tuberculosis 150 years ago by Robert Koch, antibiotics that are used to treat TB have always been tested first in animals that have been infected with TB. However, this method has not been a good predictor of how well the antibiotics will work in humans.
The hollow fiber system model of TB, sometimes called the 鈥済lass mouse,鈥� is used to select and evaluate possible drugs and treatment regimens before they are tested in clinical trials. This system is a tool that aids researchers in determining which drugs to combine and at what doses to effectively fight multi-drug-resistant mycobacterium tuberculosis, the causative agent of TB.
The hollow fiber system consists of a cartridge that has thousands of fibers running through it. Nutrients for growth of the TB bacteria and antibiotics that are being tested flow through these hollow fibers. The bacteria grow in the area around the fibers. These fibers have very small pores that allow nutrients and antibiotics to pass through to the bacteria but are too small to let the bacteria get into the fibers. Different concentrations and combinations of antibiotics can be tested to determine how well they kill the bacteria.
The hollow fiber system represents a significant advancement in the development of effective TB treatments. It improves on existing methods, which do not always provide reliable information about drug dosages for clinical trials. It is the first of its kind to be qualified by the EMA as a drug development tool.
鈥淭his is a significant advance over many drug development models. The 鈥榞lass mouse鈥� hollow fiber model has now been found to have a forecasting accuracy of within 94 percent of the clinical values that have been observed later in TB clinical trials. The development of the model has been a team effort, and I have been lucky to be associated with these other scientists鈥� Dr. Gumbo said.
Dr. Gumbo worked with the Critical Path Institute (C-Path) in its Critical Path for TB Regimens (CPTR) group to obtain EMA approval. C-Path is an independent, non-profit organization established in 2005 whose mission is to 鈥渃atalyze the development of new approaches that advance medical innovation and regulatory science, accelerating the path to a healthier world.鈥� Dr. Gumbo is co-chair of the C-Path team that also is working to obtain FDA regulatory approval for the hollow fiber model.
TB is a worldwide pandemic, especially in developing countries. According to the Centers for Disease Control, one-third of the world鈥檚 population has active or latent TB. The disease killed 1.5 million people in 2013 and is responsible for 3 percent of deaths in low- and middle-income countries. The cases of drug-resistant TB are on the rise, with around 450,000 people in 2012 contracting TB that doesn鈥檛 respond to conventional treatment.
The approval allows for the hollow fiber system to be used in the development of TB drugs. Dr. Gumbo鈥檚 group is working to expand its uses to other clinical conditions. They are also collaborating with other BRI investigators in projects that will utilize the hollow fiber system.
Dr. Gumbo joined Baylor Research Institute last year. Prior to joining BRI, he served as the administrative director of global health research at the University of Texas Southwestern Medical Center. Before that, his lab was in Albany, NY, at the Ordway Research Institute and Albany Medical College, where he published the first work on the hollow fiber model of TB. Dr. Gumbo鈥檚 group includes four junior faculty and several other researchers. He has published seven book chapters, including the introduction to Antibiotics and the TB chapter in Goodman and Gillman, considered the 鈥渂ible鈥� of pharmacology. He has published more than 81 peer-reviewed scientific articles.
He recently mapped host immunity and bacterial physiology using RNA-sequencing in the lungs of patients with TB, demonstrating that each patient could have multiple strains of TB. Over the past five years, he has established the causal pathway on how multi-drug-resistant TB arises and identified problems with the dogma of directly observed therapy, which is a cornerstone concept in the treatment and prevention of TB.
Dr. Gumbo has a five-year plan that involves applying advanced pharmacometrics, systems pharmacology, mathematical scaling from cell populations in wet lab to populations of patients, and whole-genome solutions to infectious diseases, immunology, and cancer. He has a goal of establishing Baylor Research Institute as the largest TB research center in the U.S.
Shashi Kant, PhD, and Jotam Paispanodya, MD, PhD, assistant investigators in the Center for Infectious Diseases Research and Experimental Therapeutics at BIIR, will present a seminar for World TB Day from 10:30 a.m.-noon Tuesday in the Lieberman Building鈥檚 Fordtran Conference Room, 3434 Live Oak, Dallas. They will present "Fighting Dogmas in Tuberculosis: The Glass mouse and in silico clinical trial simulations to optimize therapy for multi-drug resistant tuberculosis."
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