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Spinal 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.
Materials and methods
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.
VL and AB contributed equally.
Contributors VL and AB contributed to the writing of the manuscript, statistical analysis, data acquisition and data analysis. LZ, BM, HZ, AJH, CR, LG and MGH contributed to the critical revision of the manuscript. AM and PF contributed to the design and conceptualisation of the study and the critical revision of the manuscript.
Funding Study Funded by the NIHR UCLH Biomedical Research Centre Grant #BRC279566.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval Ethical approval was obtained from the East London and the City Research Ethics Committee (09/H0703/27) and the Ethical Review Panel of UCL Institute of Neurology (PPL PE83401B1).
Provenance and peer review Not commissioned; externally peer reviewed.