Description du projet
Modèle innovant de cerveau-organoïde non animal pour la recherche sur la neurodégénérescence
Le vieillissement de la population européenne confronte la société à une augmentation croissante des maladies neurodégénératives associées à la démence et à la perte des fonctions motrices dans le cas de la maladie de Parkinson. Le projet OpenMIND, financé par l’UE, vise à introduire un concept innovant de modélisation des maladies, appelé connectoïdes. Il représentera un modèle optoélectronique humain multirégional in vitro de connectoïdes formés par des organoïdes cérébraux reliés par des voies d’hydrogel pour la signalisation fonctionnelle axonale. Chaque organoïde contiendra des neurones spécifiques contrôlés par la lumière ainsi que des électrodes pénétrantes et des guides d’ondes pour surveiller la signalisation des neurotransmetteurs à l’intérieur des organoïdes et entre eux. Ce modèle révolutionnaire permettra de visualiser et d’évaluer en temps réel les réponses de certaines régions du cerveau à un traitement donné.
Objectif
A major challenge facing Europe is its ageing population and associated increase in diagnosed cases of neurodegenerative diseases (NDD). Parkinson’s disease (PD) is associated with tremor and loss of motor functions due to progressive degeneration of dopaminergic neurons in the brain. This can lead to memory loss and dementia, which is associated with short- and long-term injuries and disabilities with emotional, financial, and social burdens for patients, families, and society. The exact causes and mechanisms underlying PD are still unknown and existing treatments focus on alleviating symptoms and increasing quality of life, but do not halt or reverse disease progression. Although animal models give unique possibilities to study physiological and behavioural mechanisms, drug development fails due to lack of translation to humans. Alternative non-animal NDD models is needed both in terms of better translation, but also to replace expensive and problematic animal experiments.
We will move disease modelling to a new level and replace animal models, by creating a new concept we call connectoids. We will develop an ex-vivo-type in vitro human opto-electronic multi-regional brain-organoid disease model in which connectoids are formed by precise spatial arrangement of brain organoids connected via hydrogel tracts that promote axonal pathfinding, functional connection, and signalling. By developing 1) light controllable sub-type specific neurons within regionalized brain organoids, and 2) electrodes and waveguides that can penetrate the organoids able to monitor neurotransmitter signalling inside and between the organoids, we will for the first time be able to sense how a particular brain region responds to a certain therapy and watch in real time how signals are transmitted to other brain regions. Our model will not only have health benefit, but will relieve a heavy economic burden on society, and open up for new possibilities for technological and economic development.
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HORIZON-EIC - HORIZON EIC GrantsCoordinateur
2800 Kongens Lyngby
Danemark