Blood neurofilament light chain at the doorstep of clinical application.
NEUROLOGY – NEUROIMMUNOLOGY NEUROINFLAMMATION. | AUGUST 09, 2019
Leppert D and Kuhle J.
Neurology – Neuroimmunology Neuroinflammation. DOI: https://doi.org/10.1212/NXI.0000000000000599
Multiples sclerosis (MS) is a chronic progressive disorder of the CNS with inflammatory and neurodegenerative pathomechanisms leading to various degrees of neurologic disability. In the past 2 decades, high-efficacy disease-modifying therapies (DMTs) have become available that lead to near-complete suppression of acute disease activity (relapses, lesion formation) in most patients, and only a small number of patients exhibit an aggressive disease course despite adequate use of DMTs. Here, immunoablation followed by stem cell transplantation (SCT) has emerged in recent years as an efficacious approach to stop acute disease activity, based on the concept of a reset of the immune system. However, DMTs show minimal effect on the course of progression. Accordingly, 30% (7/23) of patients continue to experience clinical progression and additional brain atrophy as its MRI equivalent 12 months after SCT.1
Neurofilaments are intracellular cytoskeletal proteins that are categorized according to their molecular weight in light, medium, and heavy chain types. Neuronal damage results in leaking of this protein into the extracellular space and eventually into CSF and blood. Neurofilament light chain (NfL) has been established in recent years as a biomarker (1) to quantify acute disease activity, (2) to monitor therapy response, and (3) to predict the course of disability and of brain and spinal cord atrophy2,–,6 in pharmacologically treated relapsing-remitting MS (RRMS) and progressive MS (PMS). Based on the strong correlation between CSF and plasma or serum measures, NfL is now at the doorstep to become the first biomarker that is applicable in clinical routine setting for longitudinal measurements based on blood sampling, a minimally invasive procedure.
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