Individualized early risk assessment for heart diseases

Ziel

Heart failure (HF) is the common end-stage of different medical conditions. It is the only growing cardiovascular disease and its prognosis remains worse than that of many malignancies. The lack of evidence-based treatment for patients with diastolic HF (HFpEF) exemplifies that the current “one for all” therapy has to be advanced by an individualized approach. Inherited cardiomyopathies can serve as paradigmatic examples of different HF pathogenesis. Both gain- and loss-of-function mutations of the same gene cause disease, calling for disease-specific agonism or antagonism of this gene´s function. However, mutations alone do not predict the severity of cardiomyopathies nor therapy, because their impact on cardiac myocyte function is modified by numerous factors, including the genetic context. Today, patient-specific cardiac myocytes can be evaluated by the induced pluripotent stem cell (hiPSC) technology. Yet, unfolding the true potential of this technology requires robust, quantitative, high content assays. Our recently developed method to generate 3D-engineered heart tissue (EHT) from hiPSC provide an automated, high content analysis of heart muscle function and the response to stressors in the dish. The aim of this project is to make the technology a clinically applicable test. Major steps are (i) in depths clinical phenotyping and genotyping of patients with cardiomyopathies or HFpEF, (ii) follow-up of the clinical course, (iii) generation of hiPSC lines (40 patients, 40 healthy controls), and (iv) quantitative assessment of hiPSC-EHT function under basal conditions and in response to pro-arrhythmic or cardio-active drugs and chronic afterload enhancement. The product of this study is an SOP-based assay with standard values for hiPSC-EHT function/stress responses from healthy volunteers and patients with different heart diseases. The project could change clinical practice and be a step towards individualized risk prediction and therapy of HF.

Wissenschaftliches Gebiet

Finanzierungsplan

ERC-AG - ERC Advanced Grant

Gastgebende Einrichtung

UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF

EU-Beitrag

€ 2 494 728,00

Adresse

Martinistrasse 52
20251 Hamburg
Deutschland

Region

Hamburg Hamburg Hamburg

Aktivitätstyp

Higher or Secondary Education Establishments

Kontakt Verwaltung

Frank Neumann (Mr.)

Hauptforscher

Thomas Hans Eschenhagen (Prof.)

Links

Die Organisation kontaktieren Website

Gesamtkosten

Keine Daten

Begünstigte (1)