Therapeutic Utility of renalase and renalase peptides in cisplatin-mediated renal

DESCRIPTION (provided by applicant): Cisplatin is a cornerstone therapy for a number of cancers including testicular, bladder, ovarian and lung. It is also used to treat cancers in children. In all cases there is a high incidence of acute kidney injury (AKI) that can also lead to later stage kidney damage. This risk limits its use. We have found in pilot studies that renalase, or peptide fragments of renalase, offers the innovative potential to limit or treat this damage, thereby improving the safety and utility of cisplatin and potentially resulting in better outcomes. This proposal will prioritize the best clinical candidate for later stage development and proof of concept clinical trials in patients. Renalase, a secreted flavin adenine dinucleotide (FAD) dependent amine oxidase, is synthesized by the renal proximal tubule, secreted in blood, preferentially metabolizes epinephrine, continuously excreted in urine in the basal state. We have shown renalase deficiency (renalase KO vs Wild type [WT] mice