In the context of Friedreich’s ataxia, we have developed different neural cell models to study the molecular mechanisms of the neurodegenerative process triggered by frataxin deficiency. These studies have allowed us to identify processes such as iron-sulfur centre deficiency, a decrease in some mitochondrial respiratory chain complexes, the generation of reactive oxygen species, increased DNA damage, activation of the p53 protein, and activation of apoptosis as crucial elements in neurodegeneration. In addition, we have demonstrated an additional, very important role of astrocyte activation that contributes to the neurodegenerative process through neuroinflammatory and neurotoxic processes.

Furthermore, we are also using our cellular models to test possible therapeutic strategies with an emphasis on finding molecules (drugs or genes) capable of compensating for the functional deficits induced by frataxin deficiency or capable of efficiently increasing frataxin expression. In particular, we are paying special attention to neurotrophic factors and drugs capable of stimulating the production and/or signalling of these factors. Our group has been the first to discover that brain-derived neurotrophic factor (BDNF) has the ability to inhibit neurodegeneration induced by frataxin deficiency. We have also found that SAG, an agonist of the SHH pathway, decreases the activation of frataxin-deficient astrocytes and the secretion of proinflammatory cytokines.
Our group has also been a pioneer in the development of gene therapy strategies for Friedreich’s ataxia by introducing correct copies of the frataxin gene through the administration of herpesviral vectors carrying the cDNA or the complete genomic “locus” of frataxin.
Currently our group is focused on the characterization of neurodegeneration in the cerebellum of a new mouse model of Friedreich’s ataxia. This mouse model will also be very useful for testing possible therapeutic strategies.
In collaboration with the group of Dr. Tiago Fernandes and Dr. Joaquim Cabral, from the Institute of Bioengineering of the University of Lisbon, we are also exploring the generation of human cerebellar organoids as a new experimental model of Friedreich’s ataxia. For this purpose we are using iPS cells derived from fibroblast biopsies from healthy subjects and patients with Friedreich’s ataxia.
In the area of ​​transfer, our group has had research contracts with the biopharmaceutical company Minoryx evaluating possible drugs in our Friedreich’s ataxia models.
Our group also collaborates with the Federation of Ataxias of Spain (FEDAES) by disseminating advances in research among patients and family members.
In addition to our research activity, we are strongly committed to improving and innovating the teaching/learning of Biomedicine, the dissemination of advances in biomedical research and its bioethical and social implications.
Javier Diaz-Nido teaches mainly in the Bachelor’s Degree in Biochemistry and the Master’s Degree in Molecular Biomedicine at the Autonomous University of Madrid. He is also a member of the Institute of Human Rights, Democracy, Culture of Peace and Non-Violence (DEMOS-PAZ) of the same university.