Projektbeschreibung
RNS-Therapeutika für kardiometabolische Erkrankungen
Zu den kardiometabolischen Erkrankungen gehören Diabetes, die nichtalkoholische Fettlebererkrankung und atherosklerotische Herz-Kreislauf-Erkrankungen. Auch wenn diese Krankheiten häufig bei den Betroffenen nebeneinander bestehen, müssen die Interventionen dennoch gegen deren gemeinsame Ziele und Signalwege konzipiert werden. Das EU-finanzierte Projekt LiverTarget vereint nun Fachleute aus der ganzen Welt, um innovative Therapien gegen diese kardiometabolischen Erkrankungen zu entwickeln und zu erproben. Die Forschenden werden sich auf Ribonukleinsäure-Therapeutika (RNS) wie die kleine eingreifende RNS (siRNA) konzentrieren, um die Expression von Entzündungsgenen in der Leber stummzuschalten. Diese RNS-Moleküle werden in Komplexen mit Lipidnanopartikeln gebunden, um für eine wirksame Verabreichung an die Leber zu sorgen, in präklinischen Mausmodellen auf Wirksamkeit getestet, und für die aussichtsreichsten Kandidaten folgt die Evaluierung.
Ziel
RNA Therapeutics comprise a new rapidly expanding category of drugs including small interfering RNAs (siRNA) and messenger RNAs (mRNA) that have attracted tremendous interest recently due to their first in-class drug approvals and notable success of the mRNA vaccines in the clinic.
Obesity, diabetes, non-alcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD), in turn, are highly prevalent devastating diseases of our times despite available medicines, accounting for more than one in two deaths worldwide. They frequently co-exist, in the same patient, and constitute independent risk factors for each other; yet, unified approaches directed against common targets and shared mechanisms are lacking.
LiverTarget aims at exploiting Partners years of research in the field of cardiometabolic research, the identification of ceramide pathways and inflammatory targets, and the development of novel siRNA technologies and lipid formulations, to:
1. Generate innovative siRNA pools and synthetic mRNAs to regulate ceramide and inflammatory targets in the liver.
2. Formulate them in established human-approved liver-targeting lipid nanoparticles (LNP).
3. Determine their efficacy in vivo in preclinical mouse models of obesity, diabetes, non-alcoholic fatty liver disease (NAFLD) and atherosclerosis.
4. Complete the necessary safety and toxicology evaluation of the most promising lead candidates and prepare the preclinical evaluation dossier for the European Medicines Agency (EMA).
This will result in a set of novel RNA-LNP formulations, directed against targets shared between ASCVD, diabetes and NAFLD, with demonstrated efficacy and toxicology, ready for further clinical development. It will also open up new directions of research towards the development innovative RNA therapeutics against liver targets for the treatment of cardiometabolic diseases, ultimately benefiting the patient, the society and the economy.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
HORIZON-RIA - HORIZON Research and Innovation ActionsKoordinator
33100 Tampere
Finnland