Plasma pNfH levels differentiate SBMA from ALS
2019; BMJ; Volume: 91; Issue: 2 Linguagem: Inglês
10.1136/jnnp-2019-320624
ISSN1468-330X
AutoresVittoria Lombardi, Alessandro Bombaci, Luca Zampedri, Ching‐Hua Lu, Bilal Malik, Henrik Zetterberg, Amanda Heslegrave, Carlo Rinaldi, Linda Greensmith, Michael G. Hanna, Andrea Malaspina, Pietro Fratta,
Tópico(s)Neurogenetic and Muscular Disorders Research
ResumoSpinal and bulbar muscular atrophy (SBMA), known as Kennedy disease (KD), is a slowly progressive adult-onset X-linked neuromuscular disorder with no effective treatment. It is characterised by progressive limb and bulbar muscle weakness, associated with metabolic and endocrine alterations.1 2 SBMA is caused by the expansion of a CAG repeat in exon 1 of the androgen receptor ( AR ) gene; more than 37 repeats are pathogenic.1 While the genetic test is diagnostic, biomarkers would aid the initial differential diagnosis, and furthermore, there is a strong need for disease activity and progression markers to inform effective clinical trials design. Neurofilaments (Nfs), both light and heavy chains, are now becoming a widely accepted marker of neuronal damage and a prognostic biomarker for amyotrophic lateral sclerosis (ALS) and other neurodegenerative disease.3–7 Recently, plasma neurofilament light chain (NfL) levels were unexpectedly found not to be raised in patients with SBMA.8 This finding supports other lines of evidence, including an increase in plasma muscle damage markers, myopathic changes in biopsies and a series of genetic experiments in mouse models, that point to a primary myopathic involvement in SBMA.2 9 10 We here used the highly sensitive single molecule array (SIMOA) platform to investigate plasma levels of phosphorylated neurofilament heavy chain (pNfH), another well-established marker of neuronal damage, in patients with SBMA and in a rodent model of disease. We have undertaken cross-sectional pNfH analysis using the SIMOA platform in plasma from 46 patients with SBMA, 50 patients with ALS (25 ALS-Fast and 25 ALS-Slow, as previously described)8 and 50 healthy controls (HCs) previously tested for NfL. Participant’s demographic and clinical data are summarised in figure 1A, and detailed methods and statistical analysis are listed in the online supplementary file 1. ### Supplementary data [jnnp-2019-320624supp001.pdf] Figure 1 (A) Cohort demographic, genetic information, pNfH and clinical …
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