Elamipretide treatment during pregnancy ameliorates the progression of polycystic kidney disease in maternal and neonatal mice with PKD1 mutations

Nastaran Daneshgar; Peir-In Liang; Renny S Lan; McKenna Horstmann; Lindsay Pack; Gourav Bhardwaj; Christie M Penniman; Brian T O’Neill; Dao-Fu Dai

doi:10.1016/j.kint.2021.12.006

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Elamipretide treatment during pregnancy ameliorates the progression of polycystic kidney disease in maternal and neonatal mice with PKD1 mutations

Journal article

Peer reviewed

Elamipretide treatment during pregnancy ameliorates the progression of polycystic kidney disease in maternal and neonatal mice with PKD1 mutations

Nastaran Daneshgar, Peir-In Liang, Renny S Lan, McKenna Horstmann, Lindsay Pack, Gourav Bhardwaj, Christie M Penniman, Brian T O’Neill and Dao-Fu Dai

Kidney international, Vol.101(5), pp.906-911

12/2021

DOI: 10.1016/j.kint.2021.12.006

PMCID: PMC9038630

PMID: 34953771

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https://www.ncbi.nlm.nih.gov/pmc/articles/9038630View

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Abstract

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. [Display omitted]

Pregnancy

elamipretide

mitochondria

polycystic kidney disease

Details

Title: Subtitle: Elamipretide treatment during pregnancy ameliorates the progression of polycystic kidney disease in maternal and neonatal mice with PKD1 mutations
Creators: Nastaran Daneshgar - University of Iowa
Peir-In Liang - University of Iowa
Renny S Lan - Arkansas Children’s Nutrition Center, Little Rock, AR, USA
McKenna Horstmann - University of Iowa
Lindsay Pack - Arkansas Children’s Nutrition Center, Little Rock, AR, USA
Gourav Bhardwaj - University of Iowa
Christie M Penniman - University of Iowa
Brian T O’Neill - University of Iowa
Dao-Fu Dai - University of Iowa
Resource Type: Journal article
Publication Details: Kidney international, Vol.101(5), pp.906-911
DOI: 10.1016/j.kint.2021.12.006
PMID: 34953771
PMCID: PMC9038630
NLM abbreviation: Kidney Int
ISSN: 0085-2538
eISSN: 1523-1755
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000968, name: American Heart Association, award: 858512; DOI: 10.13039/100000002, name: National Institutes of Health, award: K08 HL145138; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs, award: lO1 BXOO4468
Language: English
Date published: 12/2021
Academic Unit: Pathology; Iowa Neuroscience Institute; Radiation Oncology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984203259302771

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