Description du projet
Une comorbidité complexe de maladies neurodéveloppementales et somatiques peut avoir une cause commune
Depuis qu’ils ont cartographié l’ensemble du génome humain il y a près de 20 ans, les scientifiques ont fait d’énormes progrès dans la compréhension des bases génétiques de nombreuses maladies. Cependant, il n’y a jamais de lien direct entre un gène et une maladie. Plusieurs troubles neurodéveloppementaux apparaissent souvent ensemble et sont également associés à d’autres maladies somatiques. Cette combinaison affecte considérablement la durée et la qualité de vie d’une personne et il n’existe aucun traitement efficace. Le projet CANDY, financé par l’UE, suit une piste de variantes génétiques rares et communes qui sont partagées dans de nombreux troubles neurodéveloppementaux et la possibilité que la dérégulation immunitaire et le microbiome jouent un rôle à un moment donné. Cette étude pourrait mettre en évidence un traitement personnalisé et une réduction drastique de la souffrance chez les patients touchés.
Objectif
Neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and intellectual disability (ID) are clinically heterogeneous, often co-occur, affect ~15% of the EU population; and are associated with somatic illnesses (e.g. epilepsy, autoimmune and gastrointestinal disease) that lead to a significant increase in morbidity and mortality. For instance in ASD the combination of ID and epilepsy is associated with a reduction in lifespan of ~ 20 years; and an economic cost that is greater than cancer, stroke, or dementia. Yet, the research spend on NDDs is less than 1% of those disorders. Hence, we lack effective new treatments for NDDs and do not understand why they co-occur. There is hope, however. Recent evidence shows that rare genetic variants increasing risk for NDDs are shared, converge on final common pathways (e.g. synaptic plasticity, glutamate and GABA neurotransmission, and excitation/inhibition imbalance), and a key role is likely played by immune dysregulation. CANDY’s innovation is to test, for the first time, if NDDs, and their common mental and somatic multi-morbidity, are caused by a combination(s) of common and rare genetic variants and immune activation acting at different ‘sensitive periods’. Our multi-disciplinary team of world leading academics, patient organizations and SMEs will cost-effectively leverage existing EU-funded studies to 1) identify novel mechanisms underpinning NDDs and their multi-morbidity, 2) develop new strategies for prevention and treatment, 3) deliver novel biomarkers to guide early diagnosis, stratification and/or treatment monitoring, and 4) provide open-access databases, translational test batteries, and tools and targets for valorisation. Together we will transform the landscape for people with NDDs and make possible personalized medicine approaches that target particular mechanisms, in specific subgroups of individuals and at different life stages.
Champ scientifique
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RIA - Research and Innovation actionCoordinateur
6525 GA Nijmegen
Pays-Bas