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Open Access 07-12-2024 | Myotonic Dystrophy | Review Article

Myotonic dystrophies: an update on clinical features, molecular mechanisms, management, and gene therapy

Authors: Martina Rimoldi, Sabrina Lucchiari, Serena Pagliarani, Giovanni Meola, Giacomo Pietro Comi, Elena Abati

Published in: Neurological Sciences | Issue 4/2025

Abstract

Myotonic dystrophies (DM) encompass a group of complex genetic disorders characterized by progressive muscle weakness with myotonia and multisystemic involvement. The aim of our paper is to synthesize key findings and advancements in the understanding of DM, and to underline the multidisciplinary approach to DM, emphasizing the importance of genetic counseling, comprehensive clinical care, and symptom management. We discuss the genetic basis of DM, emphasizing the role of repeat expansions in disease pathogenesis, as well as cellular and animal models utilized for studying DM mechanisms and testing potential therapies. Diagnostic challenges, such as determining the size of disease expansions and assessing mosaicism, are elucidated alongside emerging genetic testing methods. Therapeutic strategies, mainly for DM1, are also explored, encompassing small molecules, nucleic acid-based therapies (NATs), and genome/transcriptome engineering. The challenges of such a therapeutic delivery and immunogenic response and the importance of innovative strategies, including viral vectors and AAV serotypes, are highlighted within the text. While no curative treatments have been approved, supportive and palliative care remains essential, with a focus on addressing multisystemic complications and maintaining functional independence. Continued exploration of these therapeutic advancements offers hope for comprehensive disease management and potentially curative therapies for DM1 and related disorders.

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Title: Myotonic dystrophies: an update on clinical features, molecular mechanisms, management, and gene therapy
Authors: Martina Rimoldi
Sabrina Lucchiari
Serena Pagliarani
Giovanni Meola
Giacomo Pietro Comi
Elena Abati
Publication date: 07-12-2024
Publisher: Springer International Publishing
Keywords: Myotonic Dystrophy
Myotonic Dystrophy
Drug-Induced Myotonia
Drug-Induced Myotonia
Published in: Neurological Sciences / Issue 4/2025
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-024-07826-9

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