PAF Awards $33.082.12  Research Grant

Eva Richard, PhD, Universidad Autonoma de Madrid, Spain

“Cardiomyocytes derived from induced pluripotent stem cells as a new model for therapy development in propionic acidemia”

Understanding the cellular and molecular mechanisms that occur in genetic diseases is essential for the investigation of new strategies for their prevention and treatment. In this context, induced pluripotent stem cells (iPSC) offer unprecedented opportunities for modeling human disease. One of the fundamental powers of iPSC technology lies in the competency of these cells to be directed to become any cell type in the body, thus allowing researchers to examine disease mechanisms and identify and test novel therapeutics in relevant cell types.

The main objective of this project is focused on the generation of human iPSC-derived cardiomyocytes (hiPSC-CMs) from propionic acidemia (PA) patients as a new human cellular model for the disease.In PA, cardiac symptoms, namely cardiac dysfunction and arrhythmias, have been recognized as progressive late-onset complications resulting in one of the major causes of disease mortality. Using hiPSC-CMs we will study cellular processes, such as mitochondrial function and oxidative stress which have been recognized as main contributors for PA pathophysiology. In addition, our aim is to unravel novel altered pathways using high-throughput techniques such as RNAseq and miRNA analysis. We will also examine the potential beneficial effects of an antioxidant and a mitochondrial biogenesis activator in PA cardiomyocytes. The results that derive from this project will be relevant for the disease providing insight into the affected biological processes, and thus providing tools and models for the identification of novel adjuvant treatments for PA.