Vincik LeighAnn Y, Dautel Alexandra D, Staples Abigail A, Lauck Lillian V, Armstrong Catherine J, Howard Jeffery T, McGregor David, Ahmadzadeh Shahab, Shekoohi Sahar, Kaye Alan D
School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, 71103, USA.
Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA.
Adv Ther. 2024 Apr;41(4):1338-1350. doi: 10.1007/s12325-024-02801-4. Epub 2024 Feb 20.
Duchenne muscular dystrophy (DMD) is one of the most prevalent X-linked inherited neuromuscular disorders, with an estimated incidence between 1 in 3500 and 5000 live male births. The median life expectancy at birth is around 30 years due to a rapid and severe disease progression. Currently, there is no cure for DMD, and the standard of care is mainly palliative therapy and glucocorticoids to mitigate symptoms and improve quality of life. Recent advances in phosphorodiamidate morpholino antisense oligonucleotide (PMO) technology has proven optimistic in providing a disease-modifying therapy rather than a palliative treatment option through correcting the primary genetic defect of DMD by exon skipping. However, as a result of the high variance in mutations of the dystrophin gene causing DMD, it has been challenging to tailor an effective therapy in most patients. Viltolarsen is effective in 8% of patients and accurately skips exon 53, reestablishing the reading frame and producing a functional form of dystrophin and milder disease phenotype. Results of recently concluded preclinical and clinical trials show significantly increased dystrophin protein expression, no severe adverse effects, and stabilization of motor function. In summary, viltolarsen has provided hope for those working toward giving patients a safe and viable treatment option for managing DMD. This review summarizes an overview of the presentation, pathophysiology, genetics, and current treatment guidelines of DMD, pharmacological profile of viltolarsen, and a summary of the safety and efficacy with additional insights using recent clinical trial data.
杜氏肌营养不良症(DMD)是最常见的X连锁遗传性神经肌肉疾病之一,估计在每3500至5000例活产男婴中就有1例发病。由于疾病进展迅速且严重,出生时的中位预期寿命约为30岁。目前,DMD尚无治愈方法,护理标准主要是姑息治疗和使用糖皮质激素来减轻症状并改善生活质量。磷酰二胺吗啉代反义寡核苷酸(PMO)技术的最新进展已证明有望通过外显子跳跃纠正DMD的主要基因缺陷,从而提供一种改善疾病的疗法,而非姑息治疗选择。然而,由于导致DMD的肌营养不良蛋白基因突变差异很大,为大多数患者量身定制有效疗法一直具有挑战性。维托拉森对8%的患者有效,能准确跳跃外显子53,重新建立阅读框并产生功能性肌营养不良蛋白和较轻的疾病表型。最近结束的临床前和临床试验结果显示,肌营养不良蛋白的表达显著增加,无严重不良反应,且运动功能稳定。总之,维托拉森为那些致力于为患者提供安全可行的DMD治疗方案的人带来了希望。本综述总结了DMD的临床表现、病理生理学、遗传学和当前治疗指南概述、维托拉森的药理学特征,以及使用最新临床试验数据对安全性和有效性的总结及其他见解。