Conference Coverage

Neuronal protein could be multiple sclerosis blood biomarker


– Higher levels of a neuronal protein were found in the blood of patients with relapsing-remitting multiple sclerosis than in healthy subjects in a proof-of-concept study reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Blood levels of neurofilament light chain (NfL) were 28.1 vs. 12.5 pg/mL, respectively (P less than .0001), and were also found to be higher in relapsing-remitting multiple sclerosis (RRMS) patients with greater disease activity seen on MRI.

Dr. Jens Kuhle

Indeed, as the number of gadolinium-enhancing (Gd+) lesions increased, so did the blood concentration of NfL, at 23.9 pg/mL in patients with no Gd+ lesions, 26.7 pg/mL for those with one Gd+ lesion, 33.4 pg/mL for those with two to three Gd+ lesions, and 55.9 pg/mL for those with more than three Gd+ lesions.

“These findings support a role for neurofilament light chain (NfL) as a peripheral biomarker for MS,” said the reporting investigator Jens Kuhle, MD, of University Hospital Basel (Switzerland).

“There is an urgent unmet need for reliable biomarkers of neurodegeneration, besides efforts that are being done in MRI, optical coherence tomography, and evoked potentials,” Dr. Kuhle said.

He added: “NfL is an exclusively neuronal protein. It is expressed in the cytosol of neurons, it is released upon cell injury into the CSF [cerebral spinal fluid], and obviously it also appears in the blood circulation.” NfL in the CSF thus reflects nerve damage and had been seen in patients with MS and several other neurologic diseases, including Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis.

Until recently, however, it was not possible to detect NfL in the blood, as levels are around 50 to 100 times lower than in the CSF, but Dr. Kuhle and his associates have shown that using an electrochemiluminescence immunoassay could detect increasing NfL levels with increasing disease activity (Mult Scler. 2016 Jan 11. doi: 10.1177/1352458515623365).

In the current study, a Single Molecule Array Immunoassay (Quanterix) was used. This is based on an enzyme-linked immunoassay with more than 280,000 wells and developed to be an ultrasensitive diagnostic platform to measure minute quantities of individual proteins. Dr. Kuhle noted that it had “significantly increased sensitivity to measure NfL in blood” when compared with conventional ELISA or electrochemiluminescence (Clin Chem Lab Med. 2016;54[10]:1655-61).

Two to three consecutive blood samples taken from 149 patients with RRMS participating in the phase III FREEDOMS trial were obtained and these were compared with samples from 29 similarly aged healthy individuals without MS obtained from a separate biobank.

Patients with two or more relapses in the past 24 months had significantly higher NfL levels than did those with one relapse or no relapses. Serum NfL also significantly increased with the Expanded Disability Status Scale score recorded at the time the blood samples were taken.

Furthermore, “blood NfL levels predicted subsequent brain atrophy rates,” Dr. Kuhle reported, with NfL levels at 6 months being highly predictive of brain volume changes at 24 months (P less than .0001).

And, in this preliminary dataset, patients who had been treated with fingolimod (Gilenya) versus placebo in the FREEDOMS trial had lower NfL levels at 6, 12, and 24 months.

Dr. Kuhle observed that the findings of this study were corroborated by other study data presented during the poster sessions at the ECTRIMS 2016 meeting.

The FREEDOMS trial was sponsored by Novartis. Dr. Kuhle disclosed receiving research support and consulting fees from Biogen, Novartis, and Protagen AG. He has also received speaker fees and travel expenses from Novartis and several other companies, and several of his coinvestigators were employees of Novartis.

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