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

IF 2.7 4区 医学 Q2 CLINICAL NEUROLOGY
Neurological Sciences Pub Date : 2025-04-01 Epub Date: 2024-12-07 DOI:10.1007/s10072-024-07826-9
Martina Rimoldi, Sabrina Lucchiari, Serena Pagliarani, Giovanni Meola, Giacomo Pietro Comi, Elena Abati
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引用次数: 0

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.

肌强直性营养不良症:临床特征、分子机制、管理和基因治疗的最新进展。
肌强直性营养不良症(DM)包括一组复杂的遗传性疾病,其特征是进行性肌无力伴肌强直和多系统累及。本文的目的是综合糖尿病的主要发现和进展,并强调糖尿病的多学科方法,强调遗传咨询,综合临床护理和症状管理的重要性。我们讨论了糖尿病的遗传基础,强调重复扩增在疾病发病机制中的作用,以及用于研究糖尿病机制和测试潜在治疗方法的细胞和动物模型。诊断方面的挑战,如确定疾病扩展的大小和评估嵌合体,与新兴的基因检测方法一起被阐明。研究还探讨了主要针对DM1的治疗策略,包括小分子、基于核酸的治疗(NATs)和基因组/转录组工程。本文强调了这种治疗递送和免疫原性反应的挑战以及创新策略的重要性,包括病毒载体和AAV血清型。虽然尚未批准任何治愈性治疗,但支持性和姑息治疗仍然至关重要,重点是解决多系统并发症和保持功能独立性。对这些治疗进展的持续探索为DM1和相关疾病的综合疾病管理和潜在治愈疗法提供了希望。
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来源期刊
Neurological Sciences
Neurological Sciences 医学-临床神经学
CiteScore
6.10
自引率
3.00%
发文量
743
审稿时长
4 months
期刊介绍: Neurological Sciences is intended to provide a medium for the communication of results and ideas in the field of neuroscience. The journal welcomes contributions in both the basic and clinical aspects of the neurosciences. The official language of the journal is English. Reports are published in the form of original articles, short communications, editorials, reviews and letters to the editor. Original articles present the results of experimental or clinical studies in the neurosciences, while short communications are succinct reports permitting the rapid publication of novel results. Original contributions may be submitted for the special sections History of Neurology, Health Care and Neurological Digressions - a forum for cultural topics related to the neurosciences. The journal also publishes correspondence book reviews, meeting reports and announcements.
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