Center for Gene Therapy, Nationwide Children's Hospital.
Department of Pediatrics.
Curr Opin Neurol. 2019 Oct;32(5):722-727. doi: 10.1097/WCO.0000000000000739.
The purpose of this review is to highlight updates in the standard of care recommendations for DMD, and to describe approaches to and recent advances in genetic therapies for DMD.
Treatment of DMD patients with the corticosteroids prednisone or deflazacort remains the standard of care, and recent data shows that early treatment (as young as 5 months) with a weekend dosing regimen results in measurable improvement in motor outcomes. A mutation-specific therapy directed at restoring an open reading frame by skipping exon 51 is FDA-approved, and therapies directed at other exons are in trials. Gene replacement therapy shows significant promise in animal models, and trials are underway. Genome editing has received significant attention because of results in animal models, but challenges to implementation in humans remain.
The mainstay of treatment remains meeting well defined standards of care that have been shown to influence morbidity and mortality. These include use of systemic steroids, early nocturnal ventilatory support, appropriate cardiac care and prophylaxis, and wherever appropriate, scoliosis surgery. Early and accurate molecular diagnosis, along with appropriate and multidisciplinary care, provides the best opportunity for maximum benefit of both current standard and upcoming novel therapies for boys with DMD. Among the most promising of these is AAV-based gene replacement therapy, which is currently in clinical trials.
本文旨在强调杜氏肌营养不良症（DMD）治疗标准推荐的更新，并描述 DMD 的基因治疗方法和最新进展。
使用泼尼松或地夫可特等皮质类固醇治疗 DMD 患者仍是标准治疗方法，最近的数据表明，采用周末剂量方案对 5 个月大的患儿进行早期治疗，可显著改善运动功能。一种针对外显子 51 跳跃的突变特异性治疗方法已获得美国食品和药物管理局（FDA）的批准，针对其他外显子的治疗方法正在临床试验中。基因替代疗法在动物模型中显示出巨大的潜力，临床试验正在进行中。由于在动物模型中的结果，基因编辑受到了广泛关注，但在人类中实施仍面临挑战。
目前的治疗方法仍以满足已被证明能影响发病率和死亡率的明确标准为基础。这些方法包括使用全身皮质类固醇、早期夜间通气支持、适当的心脏护理和预防措施，以及在适当情况下进行脊柱侧弯手术。早期和准确的分子诊断，以及适当的多学科护理，为男孩 DMD 提供了从当前标准治疗和即将出现的新型治疗中获得最大益处的最佳机会。其中最有前途的是基于腺相关病毒（AAV）的基因替代疗法，该疗法目前正在临床试验中。
