A biomarker is any measurable indicator that can reliably and accurately tell us about a biological state or medical condition.
As we continue to learn more about MS and utilize new technology and tools, the biomarkers we commonly look at to diagnose and monitor the disease are expanding, helping us both answer and ask more questions.
Biomarkers that can be measured quickly and easily — such as with a routine blood test — may prove particularly valuable in monitoring and perhaps even diagnosing MS. Two such proteins are called neurofilament light (NfL) and glial fibrillary acidic protein (GFAP).
Neurofilament Light: Neurofilaments are proteins that help form the structure of axons, the long, cable-like parts of a nerve cell. When MS attacks the myelin sheath protecting the nerve, axons become damaged, and this damage leads to neurofilaments being released into the cerebrospinal fluid (CSF). While there are several types of neurofilaments – light, medium and heavy — in MS, we’re particularly concerned with neurofilament light (NfL), because we know it can be used as an indicator of inflammatory damage in the central nervous system.
Glial fibrillary acidic protein: GFAP is another type of protein filament that’s normally found in astrocytes, cells that play a critical role in the CNS by protecting and ensuring healthy function of the neurons. When astrocytes, the major support cell in the central nervous system, become damaged, they release GFAP into the CSF.
Many MS patients, in the course of their initial diagnosis or in ongoing monitoring of their disease, have had a lumbar puncture. Also commonly called a “spinal tap,” this is a procedure where a small amount of cerebrospinal fluid is extracted from a patient for examination in the lab. A lumbar puncture is generally a very safe procedure, but it can be difficult and uncomfortable for patients. Usually a patient is given a light sedative during the procedure, and there is some recovery time – usually up to a day of bed rest — following the fluid extraction.
One of the things doctors can look for in this common test is the presence of NfL and GFAP — both reliable indicators of damage in the CNS (to axons and astrocytes, respectively). By themselves, neither are sure-fire indicators of MS — in fact, they’re associated with many diseases and injuries to the brain, ranging from brain tumors to traumatic brain injury and even stroke — but together with other diagnostic tools, they can help give us a clearer picture of what’s happening with a particular patient.
The promise of biomarker monitoring lies in the fact that these filaments can also be detected in the blood plasma. This could mean that a simple blood test, instead of the more invasive and disruptive lumbar puncture, could be used to examine and monitor a patient’s NfL and GFAP levels.
Ongoing studies at the Rocky Mountain MS Center and elsewhere seek to determine the correlation between biomarkers in the spinal fluid and biomarkers in the blood plasma, to find a reliable connection between the two.
Complicating matters is the fact that there are more variables when looking at biomarkers in the blood. For example, people with a larger body size also have a larger volume of blood. While spinal fluid gives us a fairly reliable measure regardless of body size, the amount of a certain biomarker can be diluted in someone with more blood volume, which impacts the reliability of such testing.
We also understand that the presence of certain biomarkers in CSF and blood plasma naturally increase with age, perhaps due to the gradual brain atrophy we all experience as we get older, or the normal weakening of the blood-brain barrier over time. Kidney function may also affect the measurement. However, these biomarkers offer at least the potential to accurately monitor disease activity in a quick and non-invasive way. With simple blood tests, NfL and/or GFAP levels could one day be a standard tool to tell doctors if a patient’s MS activity is increasing or decreasing, how well a patient is responding to a newly-prescribed drug, or even how well a patient is doing if they’ve decided to discontinue their MS medication.
Research continues aimed at measuring the reliability of these biomarkers, as well as developing guidelines that might compensate for these differences in blood volume, age, and other potential variables.