Description du projet
Une thérapie injectable, ciblée et photoactivée pour l’hyperinsulinisme congénital
Les cellules de l’organisme sont «alimentées» par le glucose produit par la digestion des hydrates de carbone. Lorsque la glycémie augmente, les cellules bêta du pancréas libèrent de l’insuline qui permet à l’organisme d’absorber le glucose. Une glycémie trop élevée ou trop faible peut entraîner de graves problèmes. L’hyperinsulinisme congénital est une affection des nouveau-nés et des nourrissons causée par une surproduction d’insuline, qui peut être responsable de taux de glycémie dangereusement bas et de lésions cérébrales liées à l’hypoglycémie. Il n’existe actuellement aucune thérapie qui ne s’accompagne pas d’effets secondaires graves, de problèmes de santé persistants et d’une charge économique considérable. Le projet LightCure, financé par l’UE, entend démontrer la capacité de sa thérapie photodynamique ciblée injectable à tuer les cellules bêta hyperfonctionnelles de manière sûre et efficace, permettant aux bébés et à leurs familles de mener une vie normale.
Objectif
Congenital hyperinsulinism (CHI) is a group of rare diseases of newborns and infants with functionally defective nonneoplastic beta-cells that cause hypoglycemia and severe morbidity through oversecretion of insulin. CHI is a major cause of hypoglycemic brain injury with intellectual disability, epilepsy and cerebral palsy. As no registered causal therapy exists, management of CHI aims at increasing blood glucose levels causing severe side effects in all patients while life-threatening frequent hypoglycaemias remain. Removal of hyperfunctioning beta cells by pancreatectomy leads to insulin dependent diabetes mellitus (IDDM) and maldigestion of food, changing one disease for another with severe secondary morbidity. Management of CHI is choosing between evils and symptomatic management is partially effective in only some sub-types. CHI also represents a major burden for families, because of disability but also as a result of continuous monitoring and correction of glucose levels for many years, requiring permanent alertness. Health problems and economic decline occur in most parents. A normal life is not feasible for families with babies with CHI. LightCure consortium partners have demonstrated the feasibility of selectively targeting beta cells using exendin 4 (EX) labelled with a photosensitizer (700DX) specifically binding to beta cells. This photosensitizer can be activated by light of a certain wavelength and will produce radical oxygen species leading to cell damage, a principle called targeted photodynamic therapy (tPDT). In this project we will build on existing cutting-edge technology exclusively available to the consortium partners and perform human proof of concept studies demonstrating safety and efficacy of tPDT with EX700DX. We will deliver the proof-of-concept that after injection of EX700DX, minimally invasive tPDT leads to normalization of blood glucose levels avoiding morbidity, enabling a normal life for babies with CHI and their families.
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HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinateur
6525 GA Nijmegen
Pays-Bas