Leprosy Research Support
TB Antimicrobial Acquisition & Coordinating Facility
TB Vaccine Testing & Research Materials
Sponsored by Colorado Center for AIDS Research and the Division of Infectious Diseases at the University of Colorado at Denver and Health Sciences Center, Colorado State University and National Jewish Medical and Research Center. More information is available at www.uchsc.edu/ccfar/colorado_responds.htm.
Researchers throughout Colorado are working on tuberculosis from basic scientific research into the bacterium that causes the disease to drug, vaccine and diagnostic test developments, to clinical trial design and implementation. The overall goal of the meeting is to identify, highlight and discuss collaborative opportunities across institutions for research on the prevention, diagnosis and treatment of drug-resistant TB.
Eighty Front Range investigators, researchers and physicians discussing collaborative opportunities for research on the prevention, diagnosis and treatment of drug-resistant tuberculosis are expected to attend. Speakers and participants include experts from Colorado State University, University of Colorado at Denver and Health Sciences Center, National Jewish Medical and Research Center, Denver Health, University of Colorado at Boulder and Front Range area biotech firms.
Dr. Michael Iseman: "XDR-TB, AIDS and the Future of TB Control-An Apocalyptic Tale." Michael Iseman, M.D., senior physician at National Jewish Medical and Research Center, will summarize the considerable role Colorado scientists and physicians have played in the fight against tuberculosis. He will then go on to explore the "perverse truth of unintended consequences," which have given rise to drug-resistant strains of tuberculosis in recent years, and explain how actions taken in the next few years will shape the future of the worldwide TB epidemic.
Dr. Edward Janoff: "CFAR and Building Opportunities for Colorado's Infectious Disease Community." The federally-funded Colorado Center for AIDS Research is the only integrated research program for HIV/AIDS in this region. The mission of the Colorado CFAR is to provide scientific leadership and stimulate scientific collaboration among HIV/AIDS investigators by providing institutional infrastructure and promoting scientific communication across disciplines. In addition, the CFAR will promote opportunities for training and education in AIDS research as well as the dissemination of knowledge to the community. The sponsorship of this conference by the Colorado CFAR and the Division of Infectious Diseases at the University of Colorado with active partner institutions Colorado State University, National Jewish Medical Center and CU-Boulder highlights the importance of TB and HIV and of bringing the best scientists together to develop effective strategies to confront these problems.
Dr. Charles Daley: "Drug-Resistant Tuberculosis: Diagnostic Needs and Priorities." A key to preventing and successfully treating drug-resistant tuberculosis is accurate diagnosis of tuberculosis and identification of effective drugs to treat each case. That is not happening in much of the world today, leading to increasing problems of drug-resistant tuberculosis. Dr. Daley will outline priorities and strategies for developing more effective diagnostic and drug-susceptibility tests.
Dr. Dean Crick: "Therapeutics: Targets for Early Drug Discovery." Dr. Crick will present his work on new targets for TB drug discovery and give some examples of his scientific approach toward targeting specific pathways in cell wall lipid synthesis. Crick's research investigates the structure and synthesis of the cell wall that is part of the bacterium Mycobacterium tuberculosis. This cell wall is essential for the bacterium's survival and can be targeted for the development of new anti-tuberculosis drugs.
Dr. Anne J. Lenaerts: "Preclinical Testing of Experimental Compounds against M. Tuberculosis." Dr. Lenaerts' will present an overview of preclinical testing at Colorado State University of experimental drugs against M. tuberculosis. Colorado State houses the nation's TB Drug Screening Contract of the National Institutes of Health's National Institute of Allergies and Infectious Diseases.
An expert in preclinical screening of experimental compounds against M. tuberculosis, Lenaerts' research focuses on investigating two phenomena that affect the drug responsiveness of M. tuberculosis: drug tolerance and persistence of bacilli caused by its environment. This research focuses on finding novel TB drugs that are effective against latent tuberculosis. Colorado State developed a number of laboratory tests and systems to improve and accelerate the testing of TB drugs. These technologies are used by laboratories around the globe.
Dr. Robert Horsburgh: "New Microbiologic and Immunologic Markers of Response to TB Therapy - A Critical Need." Dr. Horsburgh's presentation will examine the current state of clinical trials for tuberculosis and identify opportunities for shortening the time and reducing the numbers of patients who need to be enrolled in order to evaluate new drugs and new regimens for the treatment and prevention of tuberculosis. An important way to achieve this is by the use of surrogate markers that can reliably indicate future clinical improvement so that trials can be assessed before the eventual occurrence of these clinical endpoints. In HIV trials, the most useful surrogate marker is viral load in serum, but no similar marker has been identified for tuberculosis. Many possible microbiologic and immunologic surrogate markers of tuberculosis disease have been proposed, and these will be critically evaluated. Newly identified potential markers will also be discussed.
Dr. Charles Peloquin: "How Do These Drugs Work, Anyway? PK, PD, and Treatment Outcomes." Dr. Peloquin will review key features of antibiotic action and how this action is predicated upon adequate drug delivery. Pharmacokinetics, or PK, addresses the issue of drug delivery - exposure. Pharmacodynamics addresses the issue of what happens when the drug arrives at its target ("exposure" relative to minimal inhibitory concentration, or MIC, for example). Knowledge of these two factors facilitates drug development greatly, allowing for informed selections of doses and frequencies. Poor PK is a primary reason for candidate drug failure in early clinical trials, and aberrant PK due to malabsorption or drug-interactions is a key reason for post-marketing drug failures.
Dr. Ian Orme: "Potential for Vaccination Against Drug Resistant TB." Dr. Orme will present data on the virulence of various multi-drug resistant strains of tuberculosis in laboratory animal models, and then pose the question as to whether new vaccines being developed could inhibit these isolates.
Research in his laboratory encompasses both basic and applied investigations into the nature of cell-mediated immune response to M. tuberculosis. Vaccines developed in this laboratory have shown activity against human and bovine strains of tuberculosis. The lab studies host immunity to tuberculosis. Such studies not only provide useful information regarding the precise nature of protective immunity to tuberculosis, but also new potential therapeutic approaches.
Dr. Patrick Brennan: "Concluding Remarks: Identification of Joint Research Programs." Dr. Patrick Brennan will lead a discussion on joint research programs and funding opportunities. The precise mechanism of cell wall biogenesis of the mycobacteria is one of the great unknowns in molecular biology. His lab is involved in discovering new opportunities for drug development by working to better understand cell wall synthesis, its pathways, intermediates, enzymes and genes as potential targets for new agents against tuberculosis.