Lipidomics study of plasma from patients suggest that ALS and PLS are part of a continuum of motor neuron disorders

Abstract

Motor neuron disorders (MND) include a group of pathologies that affect upper and/or lower motor neurons. Among them, amyotrophic lateral sclerosis (ALS) is characterized by progressive muscle weakness, with fatal outcomes only in a few years after diagnosis. On the other hand, primary lateral sclerosis (PLS), a more benign form of MND that only affects upper motor neurons, results in life-long progressive motor dysfunction. Although the outcomes are quite different, ALS and PLS present with similar symptoms at disease onset, to the degree that both disorders could be considered part of a continuum. These similarities and the lack of reliable biomarkers often result in delays in accurate diagnosis and/or treatment. In the nervous system, lipids exert a wide variety of functions, including roles in cell structure, synaptic transmission, and multiple metabolic processes. Thus, the study of the absolute and relative concentrations of a subset of lipids in human pathology can shed light into these cellular processes and unravel alterations in one or more pathways. In here, we report the lipid composition of longitudinal plasma samples from ALS and PLS patients initially, and after 2 years following enrollment in a clinical study. Our analysis revealed common aspects of these pathologies suggesting that, from the lipidomics point of view, PLS and ALS behave as part of a continuum of motor neuron disorders.

Histone Deacetylase Inhibition Regulates Lipid Homeostasis in a Mouse Model of Amyotrophic Lateral Sclerosis

“…Modification of glycerophospholipid metabolism by ACY-738 is accompanied by the amelioration of motor performances, the integrity of neuromuscular junctions, and significantly increased the survival of FUS mice. Moreover, a recent study showed that ALS patients are characterized by dysregulated glycerophospholipid blood levels at an early stage of the disease and that specific glycerophospholipids species correlate with disease progression [ 24 , 76 ]. Therefore, these particular lipid alterations could serve as effective biomarkers, prognosis markers, and potent indicators for the effectiveness of new HDAC inhibitors, adding a stepping stone for the rapid development of innovative treatments.…”

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy

“…Thus, identification of a lipidomic signature may be relevant to detect potential diagnostic, prognostic, and predictive biomarkers in various diseases [33]. Moreover, the study of the concentrations of a subset of lipids in human disease can shed light into cellular processes and unravel alterations in one or more pathways [34]. Lipids can be studied by targeted or untargeted lipidomics, both using high resolution Mass Spectrometry (MS).…”

Altered Metabolic Profiles of the Plasma of Patients with Amyotrophic Lateral Sclerosis

“…Increased levels of PC C36:4 have been observed in the cerebrospinal fluid (CSF) of ALS patients [ 9 ]. By contrast, decreased levels of total PCs have been reported in the plasma of ALS patients and have shown significant increases in follow-up samples of patients [ 21 ]. Our study further elucidated the reduced plasma levels in ALS patients of 31 specific PCs, 14 of which were significantly correlated with the ALSFRS-r scores.…”