A project coordinated by the Center for Neuroscience and Cell Biology of the University of Coimbra (CNC-UC), dedicated to the study of neurodevelopmental diseases and epilepsy, with a view to developing more effective therapies, has just obtained 782 thousand euros of funding from the Foundation “ la Caixa ”under the“ Health Research 2020 ”program.
The project, entitled “MStar – Potassium channel dysfunction in models of neurodevelopmental disorders”, aims to explore links between neuropsychiatric diseases and epilepsy that allow the development of better treatments for these pathologies, since it is known that about half of the individuals affected with intellectual deficits suffer from epilepsy, and patients with schizophrenia are at increased risk of developing seizures, compared to the rest of the population.
Thus, it is thought that disorders of brain development (such as intellectual deficit and schizophrenia) and epilepsy share cellular mechanisms that may be at the root of their origin.
“Neuropsychiatric diseases are the second leading cause of years of healthy life lost due to disability, and are often aggravated by the occurrence of epilepsy. However, in most cases it is not clear how pathologies are linked”, explains Ana Luísa Carvalho, project coordinator and professor at the Department of Life Sciences (DCV) at the Faculty of Sciences and Technology of the University of Coimbra (FCTUC ).
In this sense, explains the group leader of the CNC, “in this project, we explore a mechanism for regulating neuronal activity that we believe to be compromised in some neurodevelopmental diseases, such as intellectual deficit and schizophrenia, and simultaneously be involved in increasing susceptibility to epilepsy.”
One of the bases of this investigation is based on the results of a previous study carried out by Ana Luísa Carvalho‘s team, focused on the analysis of neuronal functions, such as the excitability of neurons, which are in charge of proteins known as M channels, a family of potassium channels.
The researchers found a new mechanism for regulating neuronal excitability, through the regulation of M channels, which depends on a mutated gene in some patients with intellectual deficit disorders or schizophrenia. Thus, the funds now allocated by the “la Caixa” Foundation will allow us to seek to understand how this mechanism regulates M channels, and to test therapies aimed at dysfunctional regulatory mechanisms that may be the basis of epileptic crises.
In this three-year study, animal models of disease will be used, but also human cells “differentiated into neurons, which contain mutations associated with intellectual deficit and schizophrenia, and which increase the susceptibility to epilepsy”, says Ana Luísa Carvalho , emphasizing that the project “on the one hand, explores a new mechanism for regulating type M potassium channels, regulators of neuronal excitability, and, on the other hand, aims to understand how changes in this mechanism can link the occurrence of epilepsy to neurodevelopmental diseases. Understanding this link is essential in developing more targeted therapies.”
In addition to Ana Luísa Carvalho, the team includes Paulo Pinheiro, Irina Moreira, Ângela Inácio, Gladys Caldeira and Marina Rodrigues, also researchers at CNC-UC. The project is part of a research consortium composed of CNC-UC and the Institute for Interdisciplinary Neuroscience (IINS), from the University of Bordeaux.
The “Health Research Program” is financed by the Iberian Research and Innovación Biomedica Initiative promoted by the “la Caixa” Foundation and the Foundation for Science and Technology (FCT). The program is aimed at research and development projects in biomedicine and health and, according to the “la Caixa” Foundation, it aims to “identify and promote initiatives of scientific excellence and greater potential and impact on society, both in basic research and in clinical or translational research.”