Bernert Guenther, Hahn Andreas, Köhler Cornelia, Meyer Sascha, Schara Ulrike, Schlachter Kurt, Trollmann Regina, Walter Maggie C
Sozialmedizinisches Zentrum Süd, Kaiser-Franz-Josef-Spital mit Gottfried von Preyer'schem Kinderspital, Wien, Österreich.
Abteilung Kinderneurologie, Sozialpädiatrie und Epileptologie, Zentrum Kinderheilkunde, Justus-Liebig-Universität, Gießen, Deutschland.
Nervenarzt. 2021 Apr;92(4):359-366. doi: 10.1007/s00115-020-01019-3. Epub 2020 Nov 19.
Duchenne muscular dystrophy (DMD) is the most frequent genetic neuromuscular disease in childhood with loss of ambulation usually occurring around the age of 9-11 years.
OBJECTIVE, MATERIAL AND METHODS: Based on current guidelines and clinical trials, neuropediatric and neurological experts developed recommendations for the treatment of nonambulatory DMD patients focusing on drug treatment of adults. This advisory board was sponsored by PTC Therapeutics, the distributers of the substance ataluren.
Loss of ambulation is heterogeneously defined across clinical trials. Among others, the need of a wheelchair, ambulation without mobility aids or maximum walking distance can be suitable parameters for assessment. Treatment of DMD patients at any stage of the disease is based on supportive and symptomatic measures, which should be continued after loss of ambulation. In addition, disease-modifying drugs are available for the treatment of DMD and glucocorticoids are the usual standard of care treatment even beyond the loss of ambulation. Ataluren, a potentially dystrophin restorative, disease-modifying treatment, has been approved for patients with DMD due to a nonsense mutation (nmDMD), which applies to approximately 13% of DMD patients and is usually combined with steroids. Clinical data from the STRIDE registry demonstrated a delayed disease progression even after loss of ambulation. Currently, no reliable data are available for exon skipping approaches in adult DMD patients. The antioxidant idebenone could be an option in nonambulant adolescent patients not treated with glucocorticoids and without other therapeutic options. A combination treatment of idebenone and glucocorticoids is currently being investigated in a clinical trial. Add-on treatment with idebenone in addition to ataluren may be considered for nonambulant nmDMD patients. Some of the discussed treatment options are still in clinical trials or there are not enough data for older DMD patients; therefore, these expert recommendations correspond to evidence class IV.
杜氏肌营养不良症（DMD）是儿童期最常见的遗传性神经肌肉疾病，通常在9至11岁左右丧失行走能力。
目的、材料与方法：根据现行指南和临床试验，神经儿科和神经学专家针对非行走型DMD患者的治疗制定了建议，重点关注成人药物治疗。该咨询委员会由阿他芦醇药物的经销商PTC Therapeutics赞助。
在临床试验中，对丧失行走能力的定义存在差异。其中，是否需要轮椅、无需辅助设备行走或最大行走距离等可作为合适的评估参数。DMD患者在疾病的任何阶段的治疗都基于支持性和对症措施，在丧失行走能力后也应继续。此外，有改善疾病的药物可用于治疗DMD，即使在丧失行走能力后，糖皮质激素仍是常用的标准治疗方法。阿他芦醇是一种潜在的肌营养不良蛋白恢复性、改善疾病的治疗药物，已被批准用于因无义突变（nmDMD）导致的DMD患者，约占DMD患者的13%，通常与类固醇联合使用。STRIDE注册研究的临床数据表明，即使在丧失行走能力后疾病进展也会延迟。目前，尚无关于成人DMD患者外显子跳跃方法的可靠数据。抗氧化剂艾地苯醌可能是未接受糖皮质激素治疗且无其他治疗选择的非行走型青少年患者的一种选择。目前正在一项临床试验中研究艾地苯醌与糖皮质激素的联合治疗。对于非行走型nmDMD患者，可考虑在阿他芦醇基础上加用艾地苯醌治疗。一些讨论的治疗选择仍在临床试验中，或者老年DMD患者的数据不足；因此，这些专家建议对应证据等级IV。
