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Open AccessArticle

Circulating MyomiRs as Potential Biomarkers to Monitor Response to Nusinersen in Pediatric SMA Patients

1
Neurology IV–Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy
2
PhD Program in Neuroscience, University of Milano-Bicocca, via Cadore 48, 20900 Monza, Italy
3
Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy
4
Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy
5
The Dubowitz Neuromuscular Centre, UCL NIHR GOSH Biomedical Research Centre, Great Ormond Street Institute of Child Health, London WC1N 1EH, UK
*
Authors to whom correspondence should be addressed.
The authors contributed equally to this work.
Both senior authors.
Biomedicines 2020, 8(2), 21; https://doi.org/10.3390/biomedicines8020021
Received: 24 December 2019 / Revised: 21 January 2020 / Accepted: 23 January 2020 / Published: 26 January 2020
(This article belongs to the Section Molecular and Translational Medicine)
Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by mutations in survival motor neuron (SMN) 1 gene, resulting in a truncated SMN protein responsible for degeneration of brain stem and spinal motor neurons. The paralogous SMN2 gene partially compensates full-length SMN protein production, mitigating the phenotype. Antisense oligonucleotide nusinersen (Spinraza®) enhances SMN2 gene expression. SMN is involved in RNA metabolism and biogenesis of microRNA (miRNA), key gene expression modulators, whose dysregulation contributes to neuromuscular diseases. They are stable in body fluids and may reflect distinct pathophysiological states, thus acting as promising biomarkers. Muscle-specific miRNAs (myomiRs) as biomarkers for clinical use in SMA have not been investigated yet. Here, we analyzed the expression of miR-133a, -133b, -206 and -1, in serum of 21 infantile SMA patients at baseline and after 6 months of nusinersen treatment, and correlated molecular data with response to therapy evaluated by the Hammersmith Functional Motor Scale Expanded (HFMSE). Our results demonstrate that myomiR serological levels decrease over disease course upon nusinersen treatment. Notably, miR-133a reduction predicted patients’ response to therapy. Our findings identify myomiRs as potential biomarkers to monitor disease progression and therapeutic response in SMA patients. View Full-Text
Keywords: spinal muscular atrophy; nusinersen; myomiRNAs; biomarkers spinal muscular atrophy; nusinersen; myomiRNAs; biomarkers
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Bonanno, S.; Marcuzzo, S.; Malacarne, C.; Giagnorio, E.; Masson, R.; Zanin, R.; Arnoldi, M.T.; Andreetta, F.; Simoncini, O.; Venerando, A.; Gellera, C.; Pantaleoni, C.; Mantegazza, R.; Bernasconi, P.; Baranello, G.; Maggi, L. Circulating MyomiRs as Potential Biomarkers to Monitor Response to Nusinersen in Pediatric SMA Patients. Biomedicines 2020, 8, 21.

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