The search for a biomarker detectable through a blood test that is able to predict multiple sclerosis (MS) disease activity and progression and to identify whether a treatment is effective in the clinic and in clinical trials remains a challenge. A team funded by the International Progressive MS Alliance published the results of a large study that measured levels of a protein in the blood – called neurofilament light chain (NfL) – a biomarker of nerve damage (see below for ‘What is NfL’) . NfL has the potential to be used as a biomarker for MS treatment efficacy and to monitor ongoing disease activity that is below the threshold of standard clinical and MRI markers.
In this study, the team sought to establish a NfL reference database to understand NfL values in healthy populations and those in people with MS, and how these values differ by age and body weight. They assessed thousands of blood samples from the general population and from people with MS. Altogether, they assessed blood samples from 5,390 people with more than 10,000 samples from Europe and the United States, to understand what is considered normal NfL levels in different age groups. They found that NfL levels increased generally 2% per year and begins to climb at a faster rate after age 50. They also found that higher body weight was associated with lower NfL levels. Using this data, they developed a statistical model that adjusts for differences in age and body weight. They used the statistical model to assess 1,313 participants part of a Swiss MS cohort and found that they could predict risk of increased future relapses and disability worsening. Further, the team found that changes of NfL values under different therapies revealed the extent to which their MS was responding to therapy. They confirmed these findings in 4,341 participants from a Swedish MS registry.
While this work moves us a step closer to having a blood test to predict an individual’s risk of MS disease activity and detect the effectiveness of treatment, NfL as a blood test for MS is still in development. Additional research is ongoing to further understand how blood NfL levels may be impacted by other medical conditions, whether NfL levels are substantially different in diverse populations, and how this biomarker may be used as a measure of effectiveness in clinical trials.
What is neurofilament light chain - NfL?
Neurofilament light chain (NfL) is a component of nerve cells that is released into the spinal fluid and then later into the blood after nerve damage, and higher levels may reflect ongoing disease activity. Recent advances have made it possible to measure NfL in the blood, giving it added potential in a clinical setting as an MS biomarker. However, essential information about what are ‘normal’ levels in the blood and how the changing levels of NfL should be interpreted by doctors and people with MS has been missing.
References:
“Serum neurofilament light chain for individual prognostication of disease activity in multiple sclerosis: a retrospective modelling and validation study,” by Pascal Benkert, Stephanie Meier, Sabine Schaedelin, Ali Manouchehrinia, Özgür Yaldizli, Aleksandra Maceski, Johanna Oechtering, Lutz Achtnichts, David Conen, Tobias Derfuss, Patrice H. Lalive, Christian Mueller, Stefanie Müller, Yvonne Naegelin, Jorge R. Oksenberg, Caroline Pot, Anke Salmen, Eline Willemse, Ingrid Kockum, Kaj Blennow, Henrik Zetterberg, Claudio Gobbi, Ludwig Kappos, Heinz Wiendl, Klaus Berger, Maria Pia Sormani, Cristina Granziera, Fredrik Piehl, David Leppert, Jens Kuhle, for the RDB in the Swiss Multiple Sclerosis Cohort Study Group, was published in The Lancet Neurology on February 16, 2022.
About the International Progressive MS Alliance
The Alliance exists to accelerate the development of effective treatments for people with progressive forms of multiple sclerosis to improve quality of life worldwide. It is an unprecedented global collaboration of MS organizations, researchers, health professionals, the pharmaceutical industry, companies, trusts, foundations, donors and people affected by progressive MS, working together to address the unmet needs of people with progressive MS ─ rallying the global community to find solutions. Our promise is more than hope, it is progress.