Novel Free-Circulating and Extracellular Vesicle-Derived MiRNAs Dysregulated in Duchenne Muscular Dystrophy

Abstract

Aim: To perform cross-sectional and longitudinal miRNA profiling in plasma from Duchenne muscular dystrophy (DMD) subjects and find non-invasive biomarkers in DMD. Subjects/materials&methods: Plasma was collected from 14 age and sex matched controls and 46 DMD subjects. Free-circulating and extracellular vesicle (EV)-derived miRNA expression was measured by RT-qPCR. Results: Free-circulating and EVs derived miR-29c-3p and miR-133a-3p are dysregulated in DMD subjects. Free-circulating and EV-derived miR-29c-3p are reduced in DMD subjects undergoing daily corticosteroid treatment. Free-circulating miR-1-3p and miR-122-5p are longitudinally upregulated in ambulant DMD subjects. Conclusion: We detected novel free-circulating and EV-derived dysregulated miRNAs in plasma from DMD subjects and characterized the longitudinal profile of free-circulating miRNA on plasma from DMD subjects.

Keywords: :

• biomarkers
• corticosteroids
• Duchenne muscular dystrophy
• extracellular vesicles
• microRNAs
• plasma

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2020-0052

Acknowledgments

This research was performed at the Dubowitz Neuromuscular Centre (London, UK) with the collaboration of the Institute of Myology (Paris, France), the Muscular Dystrophy Research Centre (Newcastle, UK), the Leiden University Medical Center (Leiden, The Netherlands) and the UMC St Radboud (Nijmegen, The Netherlands), and supported by a grant from the Association Française Contre Les Myopathies (AFM. The MRC Centre for Neuromuscular Diseases Biobank, supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London and NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London, is also gratefully acknowledged.

Disclaimer

All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Financial & competing interests disclosure

This work was supported by the Association Française Contre Les Myopathies, grant number: AFM – 518866. V Ricotti is currently a cofounder and chief Medical Officer of DiNAQOR AG. F Munton has received consulting fees from Biogen, Italfarmaco, Pfizer, PTC Therapeutics, Roche, Sarepta Therapeutics and Wave Therapeutics; and is supported by the National Institute of Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust, and University College London. T Voit has received consulting fees from BioMarin, Debiopharm, Dynacure, Italfarmaco, PTC Therapeutics, Sarepta Therapeutics and Santhera; he is an SAB member and holds equity in Constant Pharmaceuticals; and is supported by the National Institute of Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust, and University College London. EHN reports ad hoc consultancies for BioMarin, Summit, PTC Therapeutics and Wave Therapeutics. All reimbursements were received by the LUMC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was approved by the individual countries ethics committees in UK Bromley Research Ethics committee (REC 12/LO/0442), and the ethical committee of all the other institutions. All subjects and their legal representatives provided written informed consent for the study. This study is registered with the Clinical Trial Gov website with the number NCT02780492.

Additional information

Funding

This work was supported by the Association Française Contre Les Myopathies, grant number: AFM – 518866. V Ricotti is currently a cofounder and chief Medical Officer of DiNAQOR AG. F Munton has received consulting fees from Biogen, Italfarmaco, Pfizer, PTC Therapeutics, Roche, Sarepta Therapeutics and Wave Therapeutics; and is supported by the National Institute of Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust, and University College London. T Voit has received consulting fees from BioMarin, Debiopharm, Dynacure, Italfarmaco, PTC Therapeutics, Sarepta Therapeutics and Santhera; he is an SAB member and holds equity in Constant Pharmaceuticals; and is supported by the National Institute of Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust, and University College London. EHN reports ad hoc consultancies for BioMarin, Summit, PTC Therapeutics and Wave Therapeutics. All reimbursements were received by the LUMC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.