A research consortium that brings together the University of Coimbra (UC), the University of Salamanca (USAL) and the Salamanca Biomedical Research Institute (IBSAL) is developing a research project that aims to improve the treatment of Amyotrophic Lateral Sclerosis (ALS), a rare, rapidly progressive degenerative disease for which there is no cure. The research team aims to develop a new precision medicine platform and cellular models to improve the diagnosis and future treatment of the disease.
Funded with more than 750,000 euros (757,895.46 euros) by the European Commission - under the Interreg Spain-Portugal Cross-Border Cooperation Program (POCTEP) 2021-2027 and the European Regional Development Fund (ERDF) -, The project Cooperation and technological transfer for the development of a new precision medicine platform for Amyotrophic Lateral Sclerosis (with the acronym Cross-3DTool-4ALS), will create an innovative precision medicine platform dedicated to ALS, providing new, more realistic cell models that will make it possible to study the disease better and new therapies. Precision medicine serves to improve the prevention, diagnosis and treatment of pathologies by combining the data usually used in diagnosis and treatment (such as family history and symptoms) with each person's genetic profile.
To create this platform, the Cross-3DTool-4ALS team will carry out various activities, including "optimizing and transferring knowledge of the protocols for obtaining motor neurons and skeletal muscle cells, through the laboratory-induced differentiation of stem cells present in urine, in order to obtain motor neurons and skeletal muscle cells from ALS patients and healthy people," explains Elisabete Ferreiro, a researcher at the UC Centre for Neuroscience and Cell Biology (CNC-UC).
According to the project leader, "this non-invasive approach, which results from the collection of urine and subsequent isolation of the stem cells present, represents a significant advance in research into the disease, since it is not possible to remove neurons directly from patients and healthy individuals".
"This is a major advance in ALS research, since existing models for studying the disease are limited and often based on animal models, which do not fully represent the human being. With the 3D model that we are going to develop as part of this project, we will be able to better understand the cellular and molecular mechanisms that occur in the disease and thus identify new therapeutic targets," he adds. The model that will be created by the research team will make it possible to understand how the cells interact, in a way that mimics what happens in humans.
This 3D model will then be studied in depth by the team, focusing above all on the analysis of mitochondrial function (related to mitochondria, a cell organelle involved in numerous functions such as energy production). "We hope to be able to identify significant changes in mitochondrial function in the cells obtained from the ALS patients we are going to study, which could lead to the possible identification of promising strategies for the diagnosis and treatment of the disease," the researcher points out. In this vein, one of the consortium's objectives is to "reverse mitochondrial dysfunction through antioxidants in these cells and to reverse the pathological characteristics of ALS in the 3D model that we are going to create", says Elisabete Ferreiro.
"Currently, there are gaps in the understanding of the pathophysiology of ALS, in which the diversity of possible causes for the onset of the disease and pathophysiological heterogeneity among patients results in greater difficulty in finding accurate and effective therapies, a situation that makes the development of knowledge even more relevant so that it is possible to diagnose and treat the disease, as our project proposes," the CNC-UC researcher emphasizes.
The collaboration between UC, USAL and IBSAL, as well as the involvement of medical services from Coimbra and Salamanca, will enable the transfer of knowledge between various institutions, which "will have an impact on the quality of research carried out into this disease in Portugal and Spain, with the potential to also impact other countries", emphasizes Elisabete Ferreiro. "In the long term, we believe that the technology we are developing could be used by entities directly related to health, in order to guarantee access to the best treatment for each patient," she adds.
Also participating in the Cross-3DTool-4ALS project are the Coimbra Hospital and University Center, through the Neurology Service; the Portuguese Association of Amyotrophic Lateral Sclerosis; and the Spanish Association of Amyotrophic Lateral Sclerosis. The research will run until the end of 2026.
Catarina Ribeiro e Elisabete Ferreiro
