Barth syndrome is a rare and potentially fatal X-linked disease characterized by cardiomyopathy, skeletal muscle weakness, growth delays, and cyclic neutropenia. Patients with Barth syndrome are prone to high risk of mortality in infancy and the development of cardiomyopathy with severe weakening of the immune system. Elamipretide is a water-soluble, aromatic-cationic, mitochondria-targeting tetrapeptide that readily penetrates and transiently localizes to the inner mitochondrial membrane. Therapy with elamipretide facilitates cell health by improving energy production and inhibiting excessive formation of reactive oxygen species, thus alleviating oxidative stress. Elamipretide crosses the outer membrane of the mitochondrion and becomes associated with cardiolipin, a constituent phospholipid of the inner membrane. Elamipretide improves mitochondrial bioenergetics and morphology rapidly in induced pluripotent stem cells from patients with Barth syndrome and other genetically related diseases characterized by pediatric cardiomyopathy. Data with elamipretide across multiple models of disease are especially promising, with results from several studies supporting the use of elamipretide as potential therapy for patients with Barth syndrome, particularly where there is a confirmed diagnosis of cardiomyopathy. This review highlights the challenges and opportunities presented in treating Barth syndrome cardiomyopathy patients with elamipretide and addresses evidence supporting the durability of effect of elamipretide as a therapeutic agent for Barth syndrome, especially its likely durable effects on progression of cardiomyopathy following the cessation of drug treatment and the capability of elamipretide to structurally reverse remodel the failing left ventricle at the global, cellular, and molecular level in a gradual manner through specific targeting of the mitochondrial inner membrane.

Barth 综合征是一种罕见且可能致命的 X 连锁疾病，其特征是心肌病、骨骼肌无力、生长迟缓和周期性中性粒细胞减少症。患有 Barth 综合征的患者在婴儿期死亡的风险很高，并且会发展为心肌病并伴有免疫系统的严重削弱。Elamipretide 是一种水溶性、芳香族阳离子、线粒体靶向四肽，可轻松穿透并瞬时定位于线粒体内膜。elamipretide 治疗通过改善能量产生和抑制活性氧物质的过度形成来促进细胞健康，从而减轻氧化应激。Elamipretide 穿过线粒体的外膜并与心磷脂结合，心磷脂是内膜的一种成分磷脂。Elamipretide 可迅速改善来自 Barth 综合征和其他以小儿心肌病为特征的遗传相关疾病患者的诱导多能干细胞的线粒体生物能量学和形态学。在多种疾病模型中使用 elamipretide 的数据尤其有希望，多项研究的结果支持使用 elamipretide 作为 Barth 综合征患者的潜在治疗方法，特别是在确诊为心肌病的情况下。这篇综述强调了在用 elamipretide 治疗 Barth 综合征心肌病患者时所面临的挑战和机遇，并阐述了支持 elamipretide 作为 Barth 综合征治疗剂效果持久性的证据，