The relationship between genetic defects in protein production that operate at the level of synapses in the brain and neurodevelopmental disorders characterized by cognitive deficits has been known for several years. However, a percentage of these diseases have no clear genetic causes.

A study carried out by Humanitas and the Institute of Neuroscience of the CNR, in collaboration with the Miguel Hernández University and Institute for Neuroscience, identifies the relationship between high levels of inflammation and increased expression of the MeCP2 protein for the first time. A protein involved in childhood neurodevelopmental disorders with severe physical and mental disabilities, in diseases such as Rett syndrome and MeCP2 duplication syndrome.

Professor Michela Matteoli, director of the Institute of Neuroscience at the CNR and the Neuro Center of Humanitas and coordinator of the study published in the prestigious eLife magazine, explains: “We have shown that excessive inflammation increases the levels of MeCP2, a protein involved in neurodevelopmental diseases. By blocking one of the key inflammation molecules through an interleukin-1 beta receptor antagonist drug, an anti-inflammatory agent already used in clinical practice, we have been able to correct MeCP2 levels as well as many of the synapse defects that characterize neurodevelopmental pathologies, normalizing learning defects.

This is a discovery made in a laboratory for which, at the moment, there is no clinical evidence yet.


The link between inflammation and synaptopathies

To better understand the origin of cognitive disabilities, even in the absence of a clear genetic cause, researchers focused on inflammation as one of the main factors already known for its ability to modify the risk and severity of development disorders. In particular, they wanted to define whether and how the inflammation struck the synapses generating conditions of “synaptopathy”, or synapse diseases, a term with which they currently refer to neurodevelopmental diseases.

“The development of synaptopathies – continues Prof. Matteoli – is at the basis of the altered activity of synapse control on all cognitive skills, including learning, attention, perception, and decision making. It is therefore essential to identify factors, genetic or otherwise, that may affect their function.

“This important discovery – concludes Professor Alberto Mantovani, Scientific Director of Humanitas and lecturer at Humanitas University, one of the authors of the study – could allow to reduce cognitive disabilities and improve the quality of life in young patients suffering from autoinflammatory diseases characterized by cognitive deficits.