Minou A T Verhaeg, Rosanne Govaarts, Maaike van Putten
{"title":"了解杜氏肌营养不良相关的脑部病理。","authors":"Minou A T Verhaeg, Rosanne Govaarts, Maaike van Putten","doi":"10.1242/dmm.052302","DOIUrl":null,"url":null,"abstract":"<p><p>The most common neuromuscular disorder, Duchenne muscular dystrophy (DMD), is caused by mutations in the DMD gene, resulting in a lack of dystrophin. In addition to severe and progressive muscle wasting, a subset of individuals with DMD experience, to largely varying extents, behavioural and cognitive deficits, including a lower IQ, and neurological comorbidities, such as autism spectrum disorder, obsessive compulsive disorder and attention deficit hyperactivity disorder. Neuroimaging studies in individuals with DMD have identified widespread pathology, including structural, physiological and connective alterations. DMD mouse models exhibit a number of DMD-associated behavioural traits, including anxiety, social deficits and learning disabilities, and have been used to investigate DMD brain pathology. Although there are currently no therapies to treat DMD brain pathology, genetic approaches are being developed to restore dystrophin expression. In particular, the exon skipping approach shows promise in ameliorating certain DMD-associated behavioural deficits in preclinical settings. However, the therapeutic potential of postnatal restoration of dystrophin isoforms involved in neurodevelopment is unknown. Furthermore, challenges such as low dystrophin restoration efficacy and translatability from DMD mouse models to the clinic remain to be addressed.</p>","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"18 7","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352290/pdf/","citationCount":"0","resultStr":"{\"title\":\"Understanding Duchenne muscular dystrophy-associated brain pathology.\",\"authors\":\"Minou A T Verhaeg, Rosanne Govaarts, Maaike van Putten\",\"doi\":\"10.1242/dmm.052302\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The most common neuromuscular disorder, Duchenne muscular dystrophy (DMD), is caused by mutations in the DMD gene, resulting in a lack of dystrophin. In addition to severe and progressive muscle wasting, a subset of individuals with DMD experience, to largely varying extents, behavioural and cognitive deficits, including a lower IQ, and neurological comorbidities, such as autism spectrum disorder, obsessive compulsive disorder and attention deficit hyperactivity disorder. Neuroimaging studies in individuals with DMD have identified widespread pathology, including structural, physiological and connective alterations. DMD mouse models exhibit a number of DMD-associated behavioural traits, including anxiety, social deficits and learning disabilities, and have been used to investigate DMD brain pathology. Although there are currently no therapies to treat DMD brain pathology, genetic approaches are being developed to restore dystrophin expression. In particular, the exon skipping approach shows promise in ameliorating certain DMD-associated behavioural deficits in preclinical settings. However, the therapeutic potential of postnatal restoration of dystrophin isoforms involved in neurodevelopment is unknown. Furthermore, challenges such as low dystrophin restoration efficacy and translatability from DMD mouse models to the clinic remain to be addressed.</p>\",\"PeriodicalId\":11144,\"journal\":{\"name\":\"Disease Models & Mechanisms\",\"volume\":\"18 7\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352290/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Disease Models & Mechanisms\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1242/dmm.052302\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Disease Models & Mechanisms","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1242/dmm.052302","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/1 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
The most common neuromuscular disorder, Duchenne muscular dystrophy (DMD), is caused by mutations in the DMD gene, resulting in a lack of dystrophin. In addition to severe and progressive muscle wasting, a subset of individuals with DMD experience, to largely varying extents, behavioural and cognitive deficits, including a lower IQ, and neurological comorbidities, such as autism spectrum disorder, obsessive compulsive disorder and attention deficit hyperactivity disorder. Neuroimaging studies in individuals with DMD have identified widespread pathology, including structural, physiological and connective alterations. DMD mouse models exhibit a number of DMD-associated behavioural traits, including anxiety, social deficits and learning disabilities, and have been used to investigate DMD brain pathology. Although there are currently no therapies to treat DMD brain pathology, genetic approaches are being developed to restore dystrophin expression. In particular, the exon skipping approach shows promise in ameliorating certain DMD-associated behavioural deficits in preclinical settings. However, the therapeutic potential of postnatal restoration of dystrophin isoforms involved in neurodevelopment is unknown. Furthermore, challenges such as low dystrophin restoration efficacy and translatability from DMD mouse models to the clinic remain to be addressed.
期刊介绍:
Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.