Descrizione del progetto
Sviluppo della produzione di cardiomiociti a base di cellule staminali per riparare i danni dell’arresto cardiaco
Le proteine dell’antigene leucocitario umano (HLA, Human Leukocyte Antigen) sono espresse sulla superficie cellulare e consentono al sistema immunitario di riconoscere le cellule estranee. Le cellule provenienti da donatori omozigoti per l’HLA possono essere utilizzate per terapie in pazienti con almeno un tipo di HLA. Il progetto HEAL, finanziato dall’UE, si propone di promuovere la tecnologia dei cardiomiociti derivati da cellule staminali omozigoti per l’HLA per la terapia riparativa dell’insufficienza cardiaca con un’immunosoppressione minima. Gli obiettivi includono lo sviluppo di un algoritmo di intelligenza artificiale per prevedere le risposte immunitarie individuali, l’ottimizzazione della somministrazione di prodotti cellulari e la valutazione del rischio di aritmia indotta dal trapianto in un modello animale. L’obiettivo è ottenere l’approvazione dei prodotti e dei relativi saggi e protocolli per promuovere il primo studio sull’uomo di una terapia riparativa dell’insufficienza cardiaca basata sulle cellule.
Obiettivo
HEAL will focus on general bottlenecks to induced pluripotent stem cell therapies with a particular focus on heart failure, which remains a major cause of morbidity and mortality with very few treatment options.
HLA-homozygous cell line derived cardiomyocyte aggregates offer the prospect of a restorative heart therapy applicable to large patient populations and to overcome economic barriers associated with autologous approaches. By developing solutions for their mass-production and cryopreservation we will enable allogeneic treatment with minimum requirements for immunosuppression.
Assays for assessment of immunogenicity will provide data for the development of an artificial intelligence powered algorithm to predict recipients's immune responses for personalised design of immunosuppression protocols.
A potency assay to assure product effectiveness will be developed together with assays of tumorigenicity in vitro and in vivo that meet and exceed current regulatory requirements. A genetic integrity pipeline defining the most sensitive assays for rigorous assessment will be developed and a rescue tool in the form of a biallelic suicide gene for programmed cell death will add to the safety toolbox for the therapy.
Optimisation of cell-product administration in terms of retention and engraftment, including catheter-based delivery as minimally invasive alternative to surgical application, and assessment of risks of graft-induced arrhythmia will be determined in a pig model.
Early dialogues, via established links, to the regulatory authorities will ensure proper development according to GMP requirements.
Freedom to operate and licensing strategies with a health technology and infrastructure assessment of European centres will set the scene for approval of the cell product and related assays and protocols for storage and distribution required to progress towards a first in man study of cell-based heart repair.
Campo scientifico
- natural sciencescomputer and information sciencesartificial intelligence
- medical and health sciencesclinical medicinecardiologycardiovascular diseasescardiac arrhythmia
- social sciencessociologydemographymortality
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
Parole chiave
Programma(i)
Meccanismo di finanziamento
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinatore
30625 Hannover
Germania