Research projects

Our group develops translational studies to generate and characterize relevant animal and cellular models for specific inherited metabolic diseases which are rare diseases with a clinical need to improve existing therapies. The main objective of this project is to study the specific pathophysiological mechanisms that contribute to the progression of cardiomyopathy and neurological alterations in propionic acidemia (PA), which are the main causes of mortality and morbidity in this disease. The following results were obtained during this period: 1- The cardiac tissue of the hypomorphic PA model shows alterations in energy metabolism and mitochondrial function; however, these alterations were not observed in the nervous tissue at 5 months of age. Likewise, treatment with bezafibrate (agonist of the PPAR family of transcription factors) has shown therapeutic potential by promoting an improvement in energy metabolism and mitochondrial function, as well as a partial recovery of redox homeostasis in the heart of the animal model. 2- iPSC-derived cardiomyocytes from a PCCB patient show overexpression of cardiac-specific miRNAs and alteration of the signalling pathways they regulate, including increased expression of cardiac damage markers and ion channels, increased oxidative stress, decreased mitochondrial respiration and autophagy, and lipid accumulation. 3- iPSC-derived astrocytes from a PCCA patient show a defect in maturation and functionality, mitochondrial dysfunction and dysregulation of brain-specific miRNAs. Our work shows that iPSC-derived cardiomyocytes and astrocytes are appropriate human models for further study of the pathophysiology of this disease and provide a starting point for the evaluation of new therapeutic compounds to help improve the quality of life of patients.