The IIS Aragón works on several lines of research in rare diseases with important international recognition

From the Gaucher disease and hematological neoplasms Study Group of the IIS Aragón, in collaboration with the Spanish Foundation for the Study and Therapeutics of Gaucher and other Lysosomal Diseases (FEETEG), work is being done on several lines of research on the diseases lysosomal storage (LDS)

Irene Serrano, researcher at IIS Aragón, has been recognized with the young researcher award at WORLD Symposium 2024, held in San Diego (USA) at the beginning of February, thanks to her work on Gaucher disease

On February 29, the day of the rare diseases. An important date for increase awareness and understanding of these ailments, as well as to highlight the challenges faced by people living with these conditions and their families. An anniversary that also serves as a crucial reminder about the need for continued research, timely diagnosis and equitable access to treatments for all diseases, including those that affect a small percentage of the population. The month of February becomes a crucial time to promote solidarity, inclusion and support for all people affected by rare diseases around the world.

Precisely, since Gaucher Disease and Hematological Neoplasms Study Group of the IIS Aragón, in collaboration with the Spanish Foundation for the Study and Therapeutics of Gaucher and other Lysosomal Diseases (FEETEG), work is being done in several lines of research in low frequency diseases.

The doctoral student Irene Serrano Gonzalo He is carrying out his predoctoral work in Biochemistry and Molecular Biology, in Gaucher disease. Its directors are Dr. Pilar Giraldo, president of FEETEG, Dr. Laura López de Frutos, Medical Advisor at the Azafaros company, and Dr. Pilar Mozas, her tutor at the University of Zaragoza.

La Gaucher disease, is a hereditary disease from the group of lysosomal storage diseases that affects the metabolism of glycosphingolipids (≈ 1 in every 100.000 people in the world suffer from it, although it is more common among Ashkenazi Jews). The disease is characterized by the accumulation of lipids in lysosomes., caused by a deficit in the activity of the acid β-glucosidase enzyme, which prevents the proper decomposition of cellular debris, leading to its accumulation. The accumulation affects all the cells of the body, but the most affected are the cells of the mononuclear phagocytic system, causing clinical manifestations in various areas: bone marrow, liver, spleen and other organs.

It is important bone involvement that occurs in more than 80% of patients, due to the risk of complications such as pain, necrosis, fractures and loss of bone mineral density. Taking into account that bone complications are those that have the greatest impact on the functionality and quality of life of patients, for the moment there are no good biomarkers, that is, molecules that can be detected in the blood, which do not allow knowing the state of the bone or predicting the intensity of the bone involvement that patients will develop.

Precisely, in the study developed by Irene Serrano Gonzalo, the search for epigenetic markers, determining genetic particles of micro RNAs in blood. To do this, he is studying these molecules in the blood of patients with Gaucher disease with different degrees of bone involvement. Markers that can be related to bone involvement in two senses. On the one hand, to better understand the pathophysiology of bone damage in this entity and, on the other hand, to verify whether these molecules are useful to predict the risk that patients have of suffering from serious bone disease and, therefore, prevent them from developing irreversible complications.

This work “Bone involvement in Gaucher disease, can miRNAs determine or predict the severity degree?” has been selected as an oral presentation and awarded the young researcher award, at the last WORLD Symposium 2024, held in San Diego (USA) on February 5 to 8, 2024.

In another line of research carried out by FEETEG, in the study of lysosomal storage diseases (LDS), the doctoral student in Biochemistry and Molecular Biology, Isidro Arévalo Vargas focuses his work on the development of an NGS (massive sequencing) panel for the early diagnosis of 22 EDL with some type of treatment. The work led by Dr. Pilar Giraldo, president of the FEETEG and Dr. Pilar Mozas, professor at the University of Zaragoza and head of the Sequencing and Functional Genomics Service at the CIBA. This investigation involves the identification of genetic variants associated with these diseases, allowing for a more accurate and earlier diagnosis. In addition, it is evaluating in silico tools to analyze the variants obtained in NGS, in order to improve the accuracy in classifying variants as benign, pathogenic or of uncertain significance.

Isidro Arévalo Vargas has spent a stay at the University of Leiden, under the tutelage of Prof. Hans Aerts, a researcher of excellence in the metabolism of glycosphingolipids with whom he has developed part of his research using blood drop samples as a matrix. dry to analyze lipids and study their behavior in healthy controls and patients with different EDL, using the LC-MS/MS technique (liquid chromatography coupled to tandem mass spectrometry). This methodology offers a non-invasive and effective way to monitor lipid profiles in patients, which could provide additional information for the diagnosis and monitoring of lysosomal diseases.

These works have also been presented in poster form, in the 20th^th annual WORLDsymposium in the city of San Diego, California.

In this same line, the work “Assessing the accuracy of 16 in silico predictors on 22 lysosomal storage disorders”, has been selected and awarded the third prize for the best work presented, and will be presented orally at the MENA Congress for RARE DISEASES in the city of Abu Dhabi, on May 19, 2024.