DALLAS – Neurologists soon may use a blood biomarker of axonal damage to monitor patients with multiple sclerosis (MS) and guide treatment decisions, according to a lecture delivered at ACTRIMS Forum 2019.
Dr. David Leppert
said David Leppert, MD, senior research associate in the department of neurology at University Hopsital Basel (Switzerland).
Among patients with MS, blood NfL levels predict disability, brain volume loss, and spinal cord atrophy. In addition, studies have found that blood NfL decreases in response to disease-modifying therapy (DMT) and that second-line DMTs may decrease blood NfL more than first-line DMTs do.
The establishment of normative databases and reference biomarkers may allow neurologists to use NfL in their care of individual patients, Dr. Leppert predicted at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “I am very positive that we will make a breakthrough in the next 2 or 3 years for an individual use of neurofilaments,” he said.
Response to DMT
An analysis of blood NfL levels from patients with MS and from healthy controls in two phase 3 trials of fingolimod, FREEDOMS and TRANSFORMS, provides insights into NfL’s response to DMT (Neurology. 2019 Mar 5;92[10]:e1007-15). In FREEDOMS, which compared fingolimod with placebo, “fingolimod leads to a rapid decrease of neurofilament levels, close to normality, while placebo patients continue to have high levels,” said Dr. Leppert, a coauthor of the study.
TRANSFORMS compared interferon-beta and fingolimod. “The clinical experience that fingolimod is a more potent compound than interferon is actually reflected here by the NfL results,” Dr. Leppert said. “Both compounds lead to a decrease of neurofilaments – so, a decrease of neuronal damage – but one drug is more potent than the other one.”
Similarly, data from the observational EPIC study indicate that patients who do not receive DMT have a consistent increase in NfL levels, whereas those who receive platform therapies have a slight decrease in NfL and those who receive second-line therapies have a greater decrease, Dr. Leppert said.
Decades of research
For about 20 years, researchers have studied neurofilaments in cerebrospinal fluid (CSF) as a potential biomarker for MS and other diseases, including Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and head trauma.
“What prevented the emergence of NfL to clinical practice was the inability to measure it in blood because levels are 50-100 times lower [in blood] than in CSF,” Dr. Leppert said.
The development of single molecule array (SIMOA) technology enabled researchers to show a proper correlation between levels of NfL in CSF and those in blood, Dr. Leppert said. “That is now allowing repetitive testing in an accessible fluid compartment, meaning serum or plasma,” he said.
Compared with brain MRI, NfL may provide novel insights into MS disease activity. “MRI is measuring a structural deficit of the past,” Dr. Leppert said. “NfL is measuring online, real time what axonal damage is occurring.”