Elamipretide treatment during pregnancy ameliorates the progression of polycystic kidney disease in maternal and neonatal mice with PKD1 mutations.
Elamipretide treatment during pregnancy ameliorates the progression of polycystic kidney disease in maternal and neonatal mice with PKD1 mutations.
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DOI：
10.1016/j.kint.2021.12.006
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发表时间：
2022-05
影响因子：
19.6
通讯作者：
Dai, Dao-Fu
中科院分区：
文献类型：
--
作者：
Daneshgar, Nastaran;Liang, Peir-In;Lan, Renny S.;Horstmann, McKenna M.;Pack, Lindsay;Bhardwaj, Gourav;Penniman, Christie M.;O'Neill, Brian T.;Dai, Dao-Fu
妊娠被认为会加剧常染色体显性遗传性多囊肾病(ADPKD)的囊性进展，但FDA唯一批准的治疗成人ADPKD的药物托伐普坦不推荐用于怀孕的ADPKD患者，因为它可能对胎儿造成伤害。由于怀孕本身可能增加ADPKD进展的风险，我们研究了伊拉米普肽的安全性和有效性，这是一种线粒体保护的四肽。伊拉米普利被发现可以改善怀孕的Pkd1RC/RC小鼠肾脏疾病的进展，同时还可以减弱ERK1/2的磷酸化，促进线粒体超复合体的形成。此外，还发现伊拉米普利可以通过胎盘和母乳，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。伊拉米普肽具有极好的安全性，目前正在多个II期和III期临床试验中进行测试。这些临床前研究支持伊拉米普肽治疗ADPKD的潜在临床试验，特别是对不能服用托伐普坦的患者。
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 Pkd1RC/RC 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 pre-clinical studies support a potential clinical trial of Elamipretide for the treatment of ADPKD, particularly for patients that cannot take Tolvaptan.
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影响因子：
4.8
作者：
Guyton, KZ;Liu, YS;Holbrook, NJ
通讯作者：
Holbrook, NJ
DOI：
10.1056/nejmoa1205511
发表时间：
2012-12-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
Torres VE;Chapman AB;Devuyst O;Gansevoort RT;Grantham JJ;Higashihara E;Perrone RD;Krasa HB;Ouyang J;Czerwiec FS;TEMPO 3:4 Trial Investigators
通讯作者：
TEMPO 3:4 Trial Investigators
影响因子：
9.7
作者：
Dai, Dao-Fu;Hsieh, Edward J.;Rabinovitch, Peter S.
通讯作者：
Rabinovitch, Peter S.
影响因子：
15.9
作者：
Hopp, Katharina;Ward, Christopher J.;Harris, Peter C.
通讯作者：
Harris, Peter C.
影响因子：
5.9
作者：
Daneshgar N;Baguley AW;Liang PI;Wu F;Chu Y;Kinter MT;Benavides GA;Johnson MS;Darley-Usmar V;Zhang J;Chan KS;Dai DF
通讯作者：
Dai DF