Molecular Therapy: Methods & Clinical Development (Dec 2021)
miR-223-3p and miR-24-3p as novel serum-based biomarkers for myotonic dystrophy type 1
- Demetris Koutalianos,
- Andrie Koutsoulidou,
- Chrystalla Mytidou,
- Andrea C. Kakouri,
- Anastasis Oulas,
- Marios Tomazou,
- Tassos C. Kyriakides,
- Marianna Prokopi,
- Konstantinos Kapnisis,
- Nikoletta Nikolenko,
- Chris Turner,
- Anna Lusakowska,
- Katarzyna Janiszewska,
- George K. Papadimas,
- Constantinos Papadopoulos,
- Evangelia Kararizou,
- George M. Spyrou,
- Geneviève Gourdon,
- Eleni Zamba Papanicolaou,
- Grainne Gorman,
- Andreas Anayiotos,
- Hanns Lochmüller,
- Leonidas A. Phylactou
Affiliations
- Demetris Koutalianos
- Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus
- Andrie Koutsoulidou
- Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus
- Chrystalla Mytidou
- Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus
- Andrea C. Kakouri
- The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Neurogenetics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus
- Anastasis Oulas
- The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus
- Marios Tomazou
- The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Neurogenetics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus
- Tassos C. Kyriakides
- Yale Center for Analytical Sciences, Yale School of Public Health, 300 George Street, Suite 555, New Haven, CT 06520, USA
- Marianna Prokopi
- Department of Mechanical Engineering and Materials Science and Engineering, Cyprus University of Technology, 45 Kitiou Kyprianou Str., 3041 Limassol, Cyprus; Theramir Ltd, 13 Georgiou Karaiskaki Str., 3032 Limassol, Cyprus
- Konstantinos Kapnisis
- Department of Mechanical Engineering and Materials Science and Engineering, Cyprus University of Technology, 45 Kitiou Kyprianou Str., 3041 Limassol, Cyprus
- Nikoletta Nikolenko
- National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
- Chris Turner
- National Hospital for Neurology and Neurosurgery, Queen Square, University College London Hospitals NHS Foundation Trust, London, UK
- Anna Lusakowska
- Department of Neurology, Medical University of Warsaw, Warsaw, Poland
- Katarzyna Janiszewska
- Department of Neurology, Central Hospital of Medical University of Warsaw, Warsaw, Poland
- George K. Papadimas
- Department of Neurology, Eginitio Hospital, Medical School of Athens, 74 Vasilissis Sofias, 11528 Athens, Greece
- Constantinos Papadopoulos
- Department of Neurology, Eginitio Hospital, Medical School of Athens, 74 Vasilissis Sofias, 11528 Athens, Greece
- Evangelia Kararizou
- Department of Neurology, Eginitio Hospital, Medical School of Athens, 74 Vasilissis Sofias, 11528 Athens, Greece
- George M. Spyrou
- The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus
- Geneviève Gourdon
- Inserm, Sorbonne University, Institute of Myology, Center of Research in Myology, Paris, France
- Eleni Zamba Papanicolaou
- The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Neurology Clinic D, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus
- Grainne Gorman
- Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, University of Newcastle, Newcastle, UK
- Andreas Anayiotos
- Department of Mechanical Engineering and Materials Science and Engineering, Cyprus University of Technology, 45 Kitiou Kyprianou Str., 3041 Limassol, Cyprus
- Hanns Lochmüller
- Department of Neuropediatrics and Muscle Disorders, Medical Centre–University of Freiburg, Faculty of Medicine, Freiburg, Germany; Children’s Hospital of Eastern Ontario Research Institute, Division of Neurology, Department of Medicine, The Ottawa Hospital, and Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada
- Leonidas A. Phylactou
- Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus; Corresponding author: Leonidas A. Phylactou, Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, Nicosia, Cyprus, PO Box 23462, 1683 Nicosia, Cyprus.
- Journal volume & issue
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Vol. 23
pp. 169 – 183
Abstract
Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy, primarily characterized by muscle wasting and weakness. Many biomarkers already exist in the rapidly developing biomarker research field that aim to improve patients’ care. Limited work, however, has been performed on rare diseases, including DM1. We have previously shown that specific microRNAs (miRNAs) can be used as potential biomarkers for DM1 progression. In this report, we aimed to identify novel serum-based biomarkers for DM1 through high-throughput next-generation sequencing. A number of miRNAs were identified that are able to distinguish DM1 patients from healthy individuals. Two miRNAs were selected, and their association with the disease was validated in a larger panel of patients. Further investigation of miR-223-3p, miR-24-3p, and the four previously identified miRNAs, miR-1-3p, miR-133a-3p, miR-133b-3p, and miR-206-3p, showed elevated levels in a DM1 mouse model for all six miRNAs circulating in the serum compared to healthy controls. Importantly, the levels of miR-223-3p, but not the other five miRNAs, were found to be significantly downregulated in five skeletal muscles and heart tissues of DM1 mice compared to controls. This result provides significant evidence for its involvement in disease manifestation.
