Sphingomyelin as a myelin biomarker in CSF of acquired demyelinating neuropathies

Giovanna Capodivento,Roberto Fancellu,Gianluigi Mancardi,Vito Paolo Pastore,Davide Visigalli,Angelo Schenone,Martina Garnero,Silvano Garibaldi,Michela Demetra Ferrara,Zeeshan Hamid,Andrea Armirotti,Elisabetta Capello,Carlo Serrati,Abdul Basit,Lucilla Nobbio

doi:10.1038/s41598-017-08314-1

Giovanna Capodivento, Roberto Fancellu + Show 13 more

Open Access

https://doi.org/10.1038/s41598-017-08314-1

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Abstract

Fast, accurate and reliable methods to quantify the amount of myelin still lack, both in humans and experimental models. The overall objective of the present study was to demonstrate that sphingomyelin (SM) in the cerebrospinal fluid (CSF) of patients affected by demyelinating neuropathies is a myelin biomarker. We found that SM levels mirror both peripheral myelination during development and small myelin rearrangements in experimental models. As in acquired demyelinating peripheral neuropathies myelin breakdown occurs, SM amount in the CSF of these patients might detect the myelin loss. Indeed, quantification of SM in 262 neurological patients showed a significant increase in patients with peripheral demyelination (p = 3.81 * 10 − 8) compared to subjects affected by non-demyelinating disorders. Interestingly, SM alone was able to distinguish demyelinating from axonal neuropathies and differs from the principal CSF indexes, confirming the novelty of this potential CSF index. In conclusion, SM is a specific and sensitive biomarker to monitor myelin pathology in the CSF of peripheral neuropathies. Most importantly, SM assay is simple, fast, inexpensive, and promising to be used in clinical practice and drug development.

Highlights

Fast, accurate and reliable methods to quantify the amount of myelin still lack, both in humans and experimental models
To the best of our knowledge, similar techniques are not employed in peripheral nervous system (PNS) diseases to rate the degree of myelination[5,6,7]
A growing number of studies proved several biomarkers to be associated with the pathogenesis, development, and even recovery of demyelinating neuropathies, critical issues emerge which restrict their widespread acceptance in clinical practice[16]

Summary

Introduction

Accurate and reliable methods to quantify the amount of myelin still lack, both in humans and experimental models. The overall objective of the present study was to demonstrate that sphingomyelin (SM) in the cerebrospinal fluid (CSF) of patients affected by demyelinating neuropathies is a myelin biomarker. Experience from completed and ongoing clinical trials and natural history studies confirms difficulties in detecting clinical changes for most of these disorders, making urgent the identification of sensitive-to-change outcome measures In this context, biological markers can serve many unique purposes, including confirmation of diagnosis, monitoring disease progression or treatment effects, and prediction of clinical outcome. The amount of myelin may be assessed only in the central nervous system (CNS) of human patients by sophisticated techniques[3, 4] These systems are quite expensive and require extensive time commitment and specific expertise which make them unsuitable for daily clinical practice. Cerebrospinal fluid (CSF) of patients affected by immune-mediated demyelinating neuropathies was used to demonstrate that SM identifies myelin breakdown in these patients

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