The European Medicines Agency (EMA), the equivalent of the U.S. Food and Drug Administration, has approved the use of the hollow fiber system for the development of drugs to treat and prevent tuberculosis (TB).
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 "glass mouse," 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.
"This is a significant advance over many drug development models. The 'glass mouse' 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" 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 "catalyze the development of new approaches that advance medical innovation and regulatory science, accelerating the path to a healthier world." 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's 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't respond to conventional treatment.
The approval allows for the hollow fiber system to be used in the development of TB drugs. Dr. Gumbo's 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's 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 "bible" 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's 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."
About BIIR
BIIR (www.biir.org) is the immunology component of Baylor Research Institute and is one of the top translational human immunology centers in the world. BIIR has programs in cancer vaccines, transplantation immunology, infectious diseases and inflammatory diseases. The goal of BIIR is to quickly translate important research discoveries from the 'bench to the bedside' to improve patient care and prevent the causes of diseases before they occur.
About Baylor Research Institute
Established in 1984 in Dallas, Texas, Baylor Research Institute (BRI) promotes and supports research to bring innovative treatments from the laboratory workbench to the patient bedside. To achieve this bench-to-bedside concept, BRI focuses on basic science, clinical trials, healthcare effectiveness and quality of care research. Today, BRI is conducting more than 930 active research protocols with 400 research investigators, spanning more than 22 medical specialties, and has research and development projects in areas ranging from human immunology and orphan metabolic diseases to diabetes, cardio-vascular disease and many other unmet medical needs.
About Baylor Scott & White Health
Baylor Scott & White Health, the organization formed from the 2013 merger between Baylor Health Care System and Scott & White Healthcare, is today the largest not-for-profit health care system in the state of Texas. With total assets of $9 billion* and serving a population larger than the state of Virginia, Baylor Scott & White Health has the vision and resources to provide its patients continued quality care while creating a model system for a dramatically changing health care environment. The organization now includes 49 hospitals, more than 800 access points, more than 5,800 active physicians, 35,000 employees and the Scott & White Health Plan. For More Information visit: BaylorScottandWhite.com
Source: Baylor Research Institute