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Lookup NU author(s): Cecilia Jimenez Moreno, Dr Nikoletta Nikolenko, Professor Grainne Gorman, Gabriella-Denisa Hathazi, Dr Sally Spendiff, Professor Hanns Lochmuller, Dr Andreas Roos
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany. Background and purpose: Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy and is caused by an repeat expansion [r(CUG)exp] located in the 3' untranslated region of the DMPK gene. Symptoms include skeletal and cardiac muscle dysfunction and fibrosis. In DM1, there is a lack of established biomarkers in routine clinical practice. Thus, we aimed to identify a blood biomarker with relevance for DM1-pathophysiology and clinical presentation. Methods: We collected fibroblasts from 11, skeletal muscles from 27, and blood samples from 158 DM1 patients. Moreover, serum, cardiac, and skeletal muscle samples from DMSXL mice were included. We employed proteomics, immunostaining, qPCR and ELISA. Periostin level were correlated with CMRI-data available for some patients. Results: Our studies identified Periostin, a modulator of fibrosis, as a novel biomarker candidate for DM1: proteomic profiling of human fibroblasts and murine skeletal muscles showed significant dysregulation of Periostin. Immunostaining on skeletal and cardiac muscles from DM1 patients and DMSXL mice showed an extracellular increase of Periostin, indicating fibrosis. qPCR studies indicated increased POSTN expression in fibroblasts and muscle. Quantification of Periostin in blood samples from DMSXL mice and two large validation cohorts of DM1 patients showed decreased levels in animals and diseased individuals correlating with repeat expansion and disease severity and presence of cardiac symptoms identified by MRI. Analyses of longitudinal blood samples revealed no correlation with disease progression. Conclusions: Periostin might serve as a novel stratification biomarker for DM1 correlating with disease severity, presence of cardiac malfunction and fibrosis.
Author(s): Nguyen CDL, Jimenez-Moreno AC, Merker M, Bowers CJ, Nikolenko N, Hentschel A, Muntefering T, Isham A, Ruck T, Vorgerd M, Dobelmann V, Gourdon G, Schara-Schmidt U, Gangfuss A, Schroder C, Sickmann A, Gross C, Gorman G, Stenzel W, Kollipara L, Hathazi D, Spendiff S, Gagnon C, Preusse C, Duchesne E, Lochmuller H, Roos A
Publication type: Article
Publication status: Published
Journal: Journal of Neurology
Year: 2023
Volume: 8
Issue: 5
Pages: 464-473
Online publication date: 28/02/2023
Acceptance date: 06/02/2023
Date deposited: 19/06/2023
ISSN (print): 0340-5354
ISSN (electronic): 1432-1459
Publisher: Springer Medizin
URL: https://doi.org/10.1007/s00415-023-11633-1
DOI: 10.1007/s00415-023-11633-1
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