Currently, both the medical professional press and the lay press are discussing the importance of the so-called Serum Neurofilament Light Chain value (abbreviation: sNfL). This is mainly due to a new study that was recently published under the leadership of colleagues from Basel in Lancet Neurology. It should be noted that in MS research, there is always a search for suitable biomarkers. These are measurements capable of predicting the severity or course of a patient’s MS and evaluating the response to the chosen MS therapy. A measurement is particularly attractive if it can be determined from the blood without much effort. Similar to the long-term blood sugar value (technical term HbA1c) for evaluating blood sugar control in diabetes.
Laboratory Value Neurofilament Light Chains
In MS, the determination of so-called neurofilament light chains has proven to be a promising laboratory value in recent years. Neurofilaments are components of nerve cells. If nerve cells are damaged by MS, for example, neurofilaments are released into the surrounding tissue and thus are a measure of nerve cell damage. In particular, the measurement value for neurofilament light chains (NfL) has proven to be a suitable laboratory value for the extent of damage to the central nervous system. Initially, however, neurofilaments could only be reliably detected in the spinal fluid of MS patients. Spinal fluid removal is not a practical way to obtain information about the disease. Because spinal fluid punctures are uncomfortable for patients and complex in execution.
Therefore, it was a breakthrough when, a few years ago, it became possible to detect even the smallest amounts of neurofilament light chains in blood serum using a new analysis technique (Single Molecule Array (SIMOA) technology). This made it possible to make statements about damage in the CNS by determining the serum neurofilament light chains (sNfL) through a simple blood draw. So much for the prehistory of this biomarker.
What is the value of the recently published work? Well, simply determining such a measurement value from the blood of MS patients is unfortunately not meaningful enough. To use such a value as a reliable biomarker (in this context, the term surrogate marker is also often used – a measurement value whose influence indicates the effect of a therapy on a disease), this biomarker must be validated and standardized. This is often a very long way.
For sNfL values, it has so far been possible to show at the group level that high values indicate an active disease and that MS drugs are capable of lowering the values to varying degrees. However, the absolute measurements are fraught with some problems at the individual level (i.e., for each patient). On the one hand, sNfL values are not specific to damage caused by MS. Even minor head injuries (e.g., a header in a soccer game), but also other neurological diseases, can lead to an increase in sNfL values. Furthermore, it is known that these values also increase with age.
Significance in early disease phase and during therapy adjustment
The value of the current work lies in the fact that samples from several thousand control individuals were analyzed. With their help, the measurements in MS patients were normalized with regard to the effects of aging and body weight. This now allows for a sharper distinction of pathologically elevated values at the individual level. In two independent cohorts of individuals with multiple sclerosis, the authors were able to show that the determination of the “normalized” sNFL can contribute to the identification of individual MS patients at risk for further disease activity.
From these results, a practically relevant significance for MS patients is derived – in my view, especially in the early phases of the disease and during therapy adjustment. A possible future regular determination of the sNfL value would favor a faster adjustment of the therapy choice and a personalized early therapy decision by the treating physicians – and this would be very helpful in practice. However, it should also be considered that the analysis technique is not yet widely available. Therefore, I do not find headlines like “New Hope for MS Patients” particularly helpful. After all, it ultimately comes down to nothing more and nothing less than an improvement in care towards personalized medicine, which now needs to be implemented.
