Mediation of Lipocalin-2 Suggests Therapeutic Target in Progressive MS

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Mediation of Lipocalin-2 Suggests Therapeutic Target in Progressive MS
Mediation of Lipocalin-2 Suggests Therapeutic Target in Progressive MS

Intrathecal production of lipocalin-2 (LCN2) increases in progressive multiple sclerosis (MS) and may contribute to disease progression through suppression of remyelination, according to findings from a study published in Neurology: Neuroimmunology and Neuroinflammation.

Lipocalin-2 has been implicated in impairment of central nervous system (CNS) function through the signaling of iron delivery, cell differentiation, inflammatory processes, and particularly by influencing the cellular life/death cycle leading to various pathologies.  High circulating levels of LCN2 in the blood are normal, however, passive leakage into the cerebrospinal fluid (CSF) may result in elevated levels in the intrathecal compartment that correspond to production of neurofilament light (NFL), an axonal protein that increases through all stages of MS. The presence of NFL is a relative marker of disease activity, levels of which are higher during exacerbations of relapsing-remitting MS (RRMS) and in progressive forms of the disease including secondary-progressive MS (SPMS) and primary-progressive MS (PPMS).

Progressive MS remains an area where good disease biomarkers and therapeutic options are lacking, the authors contended. "The correlation between LCN2 and neurofilament light is interesting because it is observed in a disease stage for which our knowledge about pathogenic processes is still limited,” reported the investigators, led by Faiez Al Nimer, MD, PhD, a researcher formerly from the Karolinska Institute in Stockholm, Sweden, and currently at the University of Switzerland in Zurich.

RELATED: Beyond First Line: Natalizumab vs. Fingolimod for RRMS

Dr Nimer and colleagues investigated LCN2 levels in MS patients through collection of samples from 3 different types of studies. The first was a case control study of 147 MS patients (75 RRMS, 49 SPMS, 23 PPMS) compared to 50 controls; the second study measured LCN2 levels in CSF and brain tissue microdialysates taken from 7 SPMS patients, and the third study examined a cohort of 17 PPMS patients from an open-label trial of natalizumab for effects of that drug on LCN2 levels, which produced a decrease of LCN2 of 13.9% (P < 0.0001) on average, after 60 weeks.

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