By far, one of the greatest needs in TB R&D is the identification of biomarkers. The value of biomarkers cannot be overemphasized. Briefly, we will highlight what biomarkers are, how they are used, and describe their importance and potential for significant impact for TB drug discovery.
The term ‘biomarker’ refers to a biological indicator and serves as a marker of disease. A biomarker can derive from the host in response to a disease or infection, or directly from the pathogen or disease agent. Biomarkers are used for diagnosis, (you have TB), prognosis (how your body is responding to TB infection), stratification of TB (e.g. latent vs. active infection), or most important to drug discovery, a surrogate marker/endpoint.
A surrogate endpoint is an alternate datapoint that reflects the benefit of TB drug or vaccine treatment. Current TB trials are lengthy because patients must be followed for at least 2yr post treatment to determine if the patient’s TB has relapsed, which would indicate that the drug treatment was ineffective. A TB surrogate biomarker that is sensitive to whether a patient (host) is beginning to recover and/or the elimination or killing of the bacteria would significantly reduce costs of drug trials by decreasing the duration of the drug trial. For instance, patient A in a drug trial is expected to fully recover from infection (the bacteria is in the process of elimination or is completely killed) because patient A is showing a favorable change in ‘biomarker X’ and ‘biomarker X’ has been shown to be linked to elimination of the bacteria. Whereas, patient B is the same drug trial is not responding to treatment because ‘biomarker X’ from patient B is not responding appropriately. The key to the biomarker field is, first, their discovery, and second, their rigorous validation by showing that they robustly predict a relevant clinical effect (for example, cure).
Two recent publications by Parida and Kaufmann in Drug Discovery Today and Wallis and colleagues in The Lancet highlight the current status and progress in TB biomarker research. Using multiple ‘–omics’-based approaches (e.g. proteomics, metabolomics, etc.) the identification of more valuable biomarkers for TB active verses latent and infected verses cured will hopefully soon be realized.
What value would biomarkers add to basic research in general? What biomarkers are you currently investigating? Do you think a valid biomarker can be identified? What alternate approaches would you support? Please add your thoughts and comments below.