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A High-throughput Compatible Assay to Evaluate Drug Efficacy against Macrophage Passaged Mycobacterium tuberculosis
Published on: March 24, 2017
Pre-Clinical Tools for Predicting Drug Efficacy in Treatment of Tuberculosis
Hasmik Margaryan1, Dimitrios D Evangelopoulos2, Leticia Muraro Wildner1
1UCL Centre for Clinical Microbiology, Division of Infection & Immunity, UCL, Royal Free Campus, London NW3 2PF, UK.
Abstract:
Combination therapy has, to some extent, been successful in limiting the emergence of drug-resistant tuberculosis. Drug combinations achieve this advantage by simultaneously acting on different targets and metabolic pathways. Additionally, drug combination therapies are shown to shorten the duration of therapy for tuberculosis. As new drugs are being developed, to overcome the challenge of finding new and effective drug combinations, systems biology commonly uses approaches that analyse mycobacterial cellular processes. These approaches identify the regulatory networks, metabolic pathways, and signaling programs associated with M. tuberculosis infection and survival. Different preclinical models that assess anti-tuberculosis drug activity are available, but the combination of models that is most predictive of clinical treatment efficacy remains unclear. In this structured literature review, we appraise the options to accelerate the TB drug development pipeline through the evaluation of preclinical testing assays of drug combinations.
Insights
Combination drug therapy helps combat drug-resistant tuberculosis by targeting multiple pathways and shortening treatment. Evaluating preclinical models is key to finding effective tuberculosis drug combinations.
Area of Science:
- Microbiology
- Pharmacology
- Systems Biology
Background:
- Combination therapy is crucial for tuberculosis treatment, reducing drug resistance and therapy duration.
- Systems biology approaches analyze mycobacterial processes to identify drug targets.
- Predicting clinical efficacy from preclinical models for tuberculosis drug combinations remains a challenge.
Purpose of the Study:
- To review and evaluate preclinical testing assays for tuberculosis drug combinations.
- To identify strategies for accelerating the tuberculosis drug development pipeline.
Main Methods:
- Structured literature review of preclinical testing assays for tuberculosis drug combinations.
- Analysis of systems biology approaches for identifying mycobacterial targets.
Main Results:
- Combination therapies act on diverse targets, aiding in the fight against drug-resistant tuberculosis.
- Systems biology aids in understanding tuberculosis infection and survival mechanisms.
- The predictive value of different preclinical models for clinical efficacy is under evaluation.
Conclusions:
- Optimizing preclinical models is essential for effective tuberculosis drug development.
- Accelerating the development of new tuberculosis drug combinations requires robust evaluation methods.
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