Research Decoder: Biomarkers

hThe term “biomarker” is a popular buzzword in the biomedical research world, and for good reason. Biomarkers are an indispensable part of the researcher’s and clinician’s toolkit, and offer a powerful approach to improving disease prevention, diagnosis, and management. It can also be a confusing term, and in this Research Decoder I’ll be giving you a quick 101 on biomarkers.

Biomarkers — a portmanteau of “biological” and “markers” — are signatures found in the body that can be objectively measured and can be an indicator of your health or reveal the presence or progress of a disease. For example, blood pressure can serve as a biomarker for your cardiovascular health, while blood glucose can be a biomarker for diabetes. Biomarkers come in different shapes and sizes: molecular biomarkers are measured in biological samples (e.g. blood, urine, tissue, cerebrospinal fluid, etc.), recording biomarkers are features of your vital signs (e.g. blood pressure, temperature, etc.) and imaging biomarkers are characteristics that can be detected in a biological image (e.g. X-ray, magnetic resonance imaging, etc.).

Biomarkers can also be grouped together based on their function: diagnostic markers help to identify and confirm the presence of a disease, prognostic markers predict how the disease will unfold over time, and treatment markers help clinicians monitor how a disease responds to treatment.  In recent years, the rapid growth of our understanding of molecular biology along with advances in laboratory and imaging technology have made biomarkers an essential part of clinical research and development.

In clinical trials, biomarkers are often used as surrogate endpoints; in other words, they stand in for actual clinical endpoints (key outcomes of the trial that directly measure how a drug or intervention affects the disease process, such as relapse rate or clinical disability in MS) by measuring factors that are indirectly related to a clinically meaningful outcome. The reason that biomarkers as surrogate endpoints are important is because they can often be quickly and easily measured, and can be useful indicators of the effectiveness of a treatment when observing a clinical outcome requires a long follow-up.

This raises the question: do we have any effective and reliable biomarkers for MS? MS poses a challenge in that it is a highly complex and unpredictable disease that’s hard to pin down to a specific disease mechanism and its clinical course can vary tremendously from one person to the next. Nonetheless, researchers have been working diligently on identifying and validating new MS biomarkers that can help us predict the risk of developing the disease, monitor disease activity, and predict progression of disability. Sensitive and reliable biomarkers can also provide information about the most appropriate treatment for someone living with MS; for instance, a biomarker that can tell that someone has a high risk of experiencing rapid disability progression means that they are a good candidate for speedy and aggressive treatment.

The richest pool of molecular biomarkers of MS resides in the cerebrospinal fluid (CSF), and to some extent in the blood. While sampling the blood is easier and less invasive than acquiring a CSF sample (which must be obtained by lumbar puncture, also known as a spinal tap), blood biomarkers are generally less sensitive than ones in the CSF, particularly since the CSF provides a better window into the processes happening in the central nervous system, while peripheral blood reflects changes in the body as a whole.

One of the most reliable laboratory tests for the diagnosis of MS is oligoclonal banding. Oligoclonal bands (OCBs) are composed of inflammation-related proteins called immunoglobulins that form a banding pattern when subjected to a special laboratory test; evidence of two or more OCBs in the CSF and not in the blood indicates an immune response in the central nervous system. However, OCBs on their own do not confirm a diagnosis of MS and need to be verified by additional clinical and imaging tests.

In addition to OCBs, other molecular biomarkers are also being explored, and run the gamut from markers signifying immune activation (specific chemokines and cytokines, Epstein-Barr virus antibodies, fetuin-A, etc.), genetic risk (HLA-DRB1*1501), demyelination (myelin basic protein), blood brain barrier damage (ninjurin-1, endothelin proteins, etc.) to neuroprotection (vascular endothelial growth factor-A, vitamin D) and progression (T-cell activation signature), just to name a few. Each biomarker comes with its own strengths and weaknesses, and while none of the biomarkers identified so far on their own fully capture the complexity and variability of MS, the goal is to catalogue a selection of markers that can collectively aid in the diagnosis, prognosis and treatment of MS.

In addition to molecular biomarkers, imaging markers provide a powerful and non-invasive way of mapping out sites of inflammation and injury in the brain and spinal cord. Imaging technologies like magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and others can help clinicians spot areas of local inflammation, myelin loss and damage to nerve fibres. Moreover, measures of brain atrophy (a reduction in the volume of the brain) have been put forward as a prognostic biomarker of disability progression.

Ultimately, the goal of biomarker discovery is to reliably and accurately predict who is at risk of developing MS, precisely diagnose MS, monitor disease activity, predict how the disease will progress, and determine how the disease will respond to a treatment.

Do you have any thoughts or questions about biomarkers? Leave your comment below.

References

  1. Bielkova B & Martin R. (2004) Development of biomarkers in multiple sclerosis. Brain. 127:1463-78.
  2. Harris VK & Sadiq SA. (2009) Disease biomarkers in multiple sclerosis: potential for use in therapeutic decision making. Mol Diagn Ther. 13(4):225-44.

Image credits: © Cornelius20 | Dreamstime.com – Brain Maze Photo

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