Grupo de Investigación sobre Neurobiología y Fisiopatología Molecular en Enfermedades Raras - NeuroFisER

Presentación de la unidad de investigación

Rare diseases, also known as minority or orphan diseases, are a group of pathologies with a great heterogeneity. They affect a small number of individuals, which are, in most cases, disabling and even fatal, suffering from an important lack of resources for their treatment. Our main field of study are neuromuscular diseases, and especially ataxias. Our principal objective is to determine the molecular mechanisms underlying these diseases. Thus, our group we is mainly interested in two types of ataxias: Friedreich’s ataxia (FRDA) and CANVAS Syndrome (Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome).FRDA is the most frequent clinical form of hereditary ataxias. Understanding the pathophysiology of the disease at the molecular level allows us to identify new therapeutic targets to implement more effective treatments than the current ones for Friedreich’s ataxia. To this end, we study the pathophysiology of the disease using different models. In addition, we are focused on developing new advanced gene therapy strategies using the CRISPR/Cas9 system. The most recent line of research treats with CANVAS syndrome, a recently diagnosed disabling neurological disease. Our study comprises the generation of iPSCs from skin biopsies of CANVAS patients, and their subsequent differentiation to sensory neurons to obtain a working model. The characterization of the neurons obtained, together with the genetic and clinical screening carried out by our collaborators, will allow us to better understand the pathophysiology of this disease. Finally, we are developing a line of research focused on Huntington’s disease, where we generate a series of tools to reduce the levels of mutant huntingtin as a therapeutic approach to modify the progress of the disease. Specifically, we are using nanobodies, which are the single-chain variable region of camelid antibodies, fused to ubiquitin ligase domains. This proof of concept consists of obtaining the nanobodies as therapeutic molecules with the capacity to target the mutant huntingtin towards the proteasome for its degradation.