There are limited therapeutic options available for reproductive-age women and pediatric patients with autosomal dominant polycystic kidney disease (ADPKD), since the only FDA-approved drug Tolvaptan is teratogenic at a high dose and the safety in infants and children is unclear. In this article we demonstrate that Elamipretide, a mitochondrial-targeted peptide, is safe and efficient in maternal and neonatal mice with PKD1 mutations. Interestingly, Elamipretide can pass through the placenta and breast milk and ameliorate aggressive infantile ADPKD without any observed teratogenic or harmful effect on early development. The mechanisms include better preservation of mitochondrial respiratory supercomplexes, reduction of ROS and ERK activation. The findings from this study supports a potential future clinical trial of Elamipretide for the treatment of ADPKD, particularly for patients that cannot take Tolvaptan.

Nastaran Daneshgar, a first-year student in the Experimental Pathology Ph.D. program, was lead author on the study. Co-authors include Peir-In Liang, Renny Lan, McKenna Horstmann, Lindsay Pack, Gourav Bhardwaj, Christie Penniman and Brian O’Neill.

The paper can be viewed online at:

https://www.sciencedirect.com/science/article/pii/S0085253821011649?via%3Dihub