孕期应用 Elamipretide 可改善 PKD1 基因突变的母鼠及其子代多囊肾病的进展。
Elamipretide treatment during pregnancy ameliorates the progression of polycystic kidney disease in maternal and neonatal mice with PKD1 mutations.
机构信息
Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA; Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
出版信息
Kidney Int. 2022 May;101(5):906-911. doi: 10.1016/j.kint.2021.12.006. Epub 2021 Dec 22.
Pregnancy is proposed to aggravate cyst progression in autosomal dominant polycystic kidney disease (ADPKD) but Tolvaptan, the only FDA-approved drug for adult ADPKD, is not recommended for pregnant ADPKD patients because of potential fetal harm. Since pregnancy itself may increase the risk for ADPKD progression, we investigated the safety and efficacy of Elamipretide, a mitochondrial-protective tetrapeptide. Elamipretide was found to ameliorate the progression of kidney disease in pregnant Pkd1 mice, in parallel with attenuation of ERK1/2 phosphorylation and improvement of mitochondrial supercomplex formation. Furthermore, Elamipretide was found to pass through the placenta and breast milk and ameliorate aggressive infantile polycystic kidney disease without any observed teratogenic or harmful effect. Elamipretide has an excellent safety profile and is currently tested in multiple phase II and phase III clinical trials. These preclinical studies support a potential clinical trial of Elamipretide for the treatment of ADPKD, particularly for patients that cannot take Tolvaptan.
妊娠被认为会加重常染色体显性多囊肾病（ADPKD）的囊肿进展，但托伐普坦（Tolvaptan），唯一被 FDA 批准用于成人 ADPKD 的药物，由于潜在的胎儿危害，不建议用于 ADPKD 孕妇。由于妊娠本身可能会增加 ADPKD 进展的风险，我们研究了线粒体保护四肽 Elamipretide 的安全性和疗效。研究发现，Elamipretide 可改善妊娠 Pkd1 小鼠的肾脏疾病进展，同时减轻 ERK1/2 磷酸化和改善线粒体超级复合物形成。此外，Elamipretide 被发现可以穿过胎盘和母乳，并改善侵袭性婴儿多囊肾病，没有观察到任何致畸或有害作用。Elamipretide 具有极好的安全性，目前正在进行多项 II 期和 III 期临床试验。这些临床前研究支持 Elamipretide 治疗 ADPKD 的潜在临床试验，特别是对于不能服用托伐普坦的患者。
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