Area 3

Inherited metabolic deseases

Team leader

Strategic objectives

The strategic objective of our group is to investigate the genetic and biochemical bases, as well as the physiopathological mechanisms, of a group of rare diseases called “inherited metabolic diseases or inborn errors of metabolism”. The ultimate aim is to develop new diagnostic and therapeutic strategies. On the other hand, we conduct translational research, stimulating the transfer of knowledge from basic research to the clinical practice, and vice versa.

Main lines of research

Within the general line of inherited metabolic diseases, our specific research lines are based on the following:

  1. Identification of genes responsible for Mendelian disorders in patients preselected on the basis of their clinical and biochemical characteristics; within this line we have used exome sequencing to identify genes in patients with mitochondrial respiratory chain deficiencies, organic acidurias and congenital defects of glycosylation (CDG). Recently, our group has been focused in the identification of genes involved in the biosynthesis and transport of cofactors of the mitochondrial energy metabolism (lipoic acid, thiamine, CoQ10, riboflavin and iron sulfur clusters). We aim to identify new defects to generate knowledge that could be implemented to the diagnosis and to the design therapeutic options
  2. In vitro therapeutic approaches. This line of research involves the testing of chemical and peptide libraries. Selection has been made of disease-causing stop and missense mutations previously identified by our group in a wide range of diseases. We make use of fibroblasts, pluripotent induced stem (IPS) cells and neuronal cell cultures obtained from IPS.
  3. Cerebral creatine deficiency. Our group has been a pioneer in the identification of patients with cerebral creatine deficiency. Actually, we are focused on the evaluation of different creatine derivatives with the purpose of establishing a treatment for creatine transport deficiency. These creatine uptake studies are carried out in neurons derived from IPS cells as well as in HUVEC and HBMEC cells silenced with RNA interference.
  4. Niemann-Pick type C disease. The study of this disorder has been carried out in a knock-in murine model in order to gain further knowledge of the underlying physiopathological mechanisms involved in this disease and to test different drugs with potential therapeutic activity that act in the proteosomal degradation pathways.