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Blood neurofilament light chain levels are elevated in multiple sclerosis and correlate with disease activity
Author(s): ,
J Kuhle
Affiliations:
Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel
,
C Barro
Affiliations:
Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel
,
A.H Brachat
Affiliations:
Novartis Institutes for Biomedical Research
,
M.-A Valentin
Affiliations:
Novartis Institutes for Biomedical Research
,
R Hillenbrand
Affiliations:
Novartis Institutes for Biomedical Research
,
H Kropshofer
Affiliations:
Novartis Pharma AG, Basel, Switzerland
,
L Kappos
Affiliations:
Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel
F Dahlke
Affiliations:
Novartis Pharma AG, Basel, Switzerland
ECTRIMS Online Library. Kuhle J. Sep 16, 2016; 147076; 249
Jens Kuhle
Jens Kuhle
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Abstract: 249

Type: LB Oral

Abstract Category: Late Breaking News

Background: Neuronal loss is a hallmark of disease progression and disability in multiple sclerosis (MS). Neurofilament light chains (NfL) are structural proteins in neurons. Levels of NfL in cerebrospinal fluid (CSF) have emerged as a marker of neuronal injury in MS and other CNS diseases. In contrast to CSF, serial blood samples can readily be collected, hence reliable quantification of NfL in blood would be a major stride towards a biomarker of neurodegeneration.

Objectives: Assess (i) whether NfL blood levels differ between patients with relapsing-remitting MS (RRMS) and healthy controls, (ii) whether blood NfL levels correlate with occurrence and number of gadolinium-enhancing (Gd+) lesions, T2 lesion volume, annual rate of brain atrophy (ARBA) and annual relapse rate (ARR).

Methods: Patients with RRMS (n=150) participating in a fingolimod Phase 3 clinical study were randomly selected, based on the availability of blood samples taken at days -5 up to 14 after an MRI scan, and were assigned to 4 MRI-defined activity groups (0, 1, 2-3 and >3 Gd+ lesions). NfL levels were also determined in age-matched healthy controls (n=29). NfL was quantified applying the Single Molecule Array (SIMOA) technology and antibodies from UmanDiagnostics (Umea, Sweden). Statistical analysis was done using Welch"s t-test, Spearman rank correlations and linear regression analysis.

Results: Blood NfL levels were higher in patients with RRMS (median: 28.3 pg/ml) than in healthy controls (median: 12.5 pg/ml; p< 0.0001). Median NfL levels in the 4 patient groups ranged from 23.9 to 55.9 pg/ml, increasing with incremental lesion counts (p=0.00039). A linear regression analysis revealed that NfL levels increased by 3.5 ± 0.5 pg/ml per Gd+ lesion. The median NfL level in patients with no Gd+ lesions was almost twice as high as in the healthy control group (see above; p=0.00039). NfL levels in patients correlated with the number of Gd+ lesions (r=0.54), T2 lesion volume (r=0.46), ARBA (r= -0.36) and ARR (r =0.38; all p< 0.0001).

Conclusions: NfL blood concentrations were not only higher in patients with RRMS than in healthy controls, but did also reflect the degree of acute CNS inflammation, as depicted by Gd enhancement in MRI, and correlated with other measures of focal and diffuse damage in RRMS. These findings support, at the group level, a role of blood NfL as a sensitive peripheral biomarker of neuronal injury in MS.

Disclosure: Jens Kuhle"s institution (University Hospital Basel) received and used exclusively for research support: consulting fees from Biogen, Novartis, Protagen AG; speaker fees from the Swiss MS Society, Biogen, Genzyme, Merck, Novartis, Roche; travel expenses from Merck Serono, Novartis, Roche; grants from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation, Bayer, Genzyme, Novartis, Roche.

Christian Barro has received travel support from Teva and Novartis.

Ludwig Kappos"s institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos" activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer Health Care Pharmaceuticals, CLC Behring, df-mp, Genentech, Inc., GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono Pharma, Pfizer, Receptos, F. Hoffmann-La Roche Ltd., Sanofi-Aventis, Santhera, Siemens and Teva, UCB, Xenport; royalties from Neurostatus AG; research grants from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, Novartis Research Foundation and Roche Research foundation.





Arndt Holger Brachat, Marie-Anne Valentin, Rainer Hillenbrand, David Leppert, Harald Kropshofer, and Frank Dahlke
are employees of Novartis Pharma AG

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