ISAC Award Program Application Concept

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Mitochondria therapy to restore kidney function
Rihab Bouchareb   (Philadelphia, PA)
Acute kidney injury (AKI) is a critical health condition characterized by a sudden decline in kidney function. It occurs in approximately 20%-30% of hospitalized patients. In the US, AKI is leading to high morbidity and mortality. Although AKI encompasses various etiologies, tubular injury is an early and decisive step in AKI. During hypoxia, proximal tubular cells (PTCs) undergo oxidant stress, mitochondrial damage, protein synthesis inhibition, and growth arrest. Non-treated AKI will progress to chronic kidney disease (CKD) and end-stage renal disease. Renal replacement therapy is necessary for patients with a survival of only 10%. Currently, no pharmacological or preventive strategies are available to reverse or reduce the occurrence of severe AKI or stop its progression to chronic or end-stage kidney disease, emphasizing the need for research in this area. This application will test an innovative-risky approach to restore proximal tubular cell function in an acute kidney disease mouse model. In this proposal, we will examine, in vivo, a new delivery approach of competent mitochondria to restore kidney function. We will use free green fluorescent mitochondria isolated from Pham mice and encapsulated mitochondria in platelet microparticles to assess the efficacy of the transplantation in vivo. In addition, we will examine the efficient mechanisms leading to mitochondria uptake by the recipient PTC cells in vivo. We propose a new paradigm-shifting method for treating kidney injury with mitochondria-transplant therapy. The outcomes of this new approach could significantly improve the health of AKI patients.
Data for this report has not yet been released.

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