Dr. Javier Riancho Zarrabeita a neurologist at University Hospital Marques de Valdecilla and IDIVAL has been awarded Juan María Parés Prize for the best doctoral thesis in the area of Biomedical Sciences. The jury evaluated the scientific solvency of the assignment, its innovative character as well as its applicability and ability to transfer knowledge. The awards ceremony will take place the next March 13.
Dr. Riancho has currently a Rio Hortega contract at the Department of Neurology and he is a member of the Idival’s Neurodegenerative Diseases Group. His doctoral thesis entitled “Effect of bexarotene in transgenic mice with ALS: histological and molecular study” was done in the Department of Anatomy and Cell Biology at the UC under the direction of Professors Miguel Lafarga, Maria T. Berciano and José A Berciano.
During 2012, Dr. Riancho developed this project based on the analysis of the effect of Bexarotene (retinoid agonist molecule and currently used for the treatment of some cutaneous lymphomas) in the most widespread animal model of ALS; The transgenic model SOD1G93A. Retinoids are molecules derived from vitamin A that exert their effects modulating the transcription of hundreds of genes among which are genes related to the response to stress, neuroinflammation or autophagy.
Investigations demonstrated that the treatment with bexaroteno increased the survival and preserved the neuromuscular function in more than a third of the symptomatic period of the animals. Histological studies showed that treatment with retinoids ameliorated the loss of motor neurons (neurons primarily affected in ALS) in both the presymptomatic and early symptomatic stages of the disease. Further studies revealed that these neuroprotective effects were due to the treatment improving protein metabolism (promoting a more efficient proteasomal proteolysis and modulating the autophagic response) and preserving the neuronal microenvironment by decreasing reactive astrogliosis.
Adapted from Riancho et al. Front in Cell Neuroscience 2015. The figure shows the main effects of bexarotene treatment on survival, neuromuscular function basic histology in the anterior horn of the spinal cord.
In a complementary way in his doctoral thesis, Dr. Riancho identified in both ALS and murine models of ALS a neuroprotective mechanism to the reticulum stress consisting of: i) formation of stress granules; Ii) establishment of a perinuclear domain, enriched in granular endoplasmic reticulum and nuclear folds; And iii) preserved nucleolar activity in an attempt to preserve the biogenesis of ribosomes for the synthesis of proteins essential for cell survival.
Taken from Riancho et al. Front in Cell Neuroscience 2014. The figure shows the presence of nuclear folds and a perinuclear endoplasmic reticulum domain in a patient with sporadic ALS.
Currently, Dr. Riancho continues with this line initiated 5 years ago after having signed a collaboration agreement with the company Innopharma and the University of Santiago de Compostela focused on the development of a new molecule agonist of retinoids, for the treatment of the patients with the disease.
