Assessment of the uniqueness of diabetic cardiomyopathy relative to other forms of heart failure using unbiased pheno-mapping approaches

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Domaine de recherche :
Santé
Type de financement :
H2020
Type d'instrument :
Recherche & Innovation Action
Deadline :
Jeudi 06 Septembre 2018
1ère partie : 28 février 2018
Budget total :
223,05 millions d'euros
Code de l'appel : IMI2-2017-13-01
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À noter :

Specific Challenge:

Diabetes contributes to the development of heart failure (HF) indirectly by promoting the progression of coronary artery disease and directly through the development of cardiomyopathy. Thus, diabetic patients have a 2.5-fold greater risk for HF as compared to those without diabetes. Epidemiological studies have reported a 4-fold higher prevalence of diabetes mellitus in HF patients (20%) compared to age-matched populations without HF (5%) which rises up to 40% in hospitalised HF patients. Over the last decades it became clear that there is a relationship between diabetes and HF, although not all patients with diabetes develop cardiomyopathy or evolve toward HF.

The overall objective of this topic is to determine whether diabetic cardiomyopathy is unique and distinct from the other forms of heart failure such as HFpEF (heart failure with preserved ejection fraction) or HCM (hypertrophic cardiomyopathy) by performing unbiased statistical clustering analysis from a dense phenotyping of these patient populations.

Furthermore, a better comprehension of the underlying mechanisms and clinical manifestations of diabetic cardiomyopathy will also allow the development of more translatable and predictable preclinical models to support target and drug discovery.

Scope:

The overall goal of the proposed topic is to assess the uniqueness of diabetic cardiomyopathy and to unveil the underlying mechanisms of cardiomyopathy in diabetic patients and the impact on cardio-vascular mortality in this population, which may finally allow the clustering of patients into an independent cohort. In consequence, this improved understanding of the clinical manifestations and diagnosis of diabetic cardiomyopathy as well as the linkage between the onset and disease progression with a specific signature will enable patient stratification at an early stage of the disease by clustering of patients into an independent cohort.

Expected Impact:

In terms of research and development (R&D), clinical, regulatory, healthcare practice and patient management:

  • proposals are expected to define and assess key phenotypes that characterise diabetic cardiomyopathy and could serve to establish patient diagnosis and ultimately prognosis;
  • the stratification of patients into the diabetic cardiomyopathy cluster based on pheno-mapping, supported by biomarkers specific for this group will be transformative for the clinical management of these patients;
  • furthermore, novel pre-clinical models with improved knowledge on the translatability to humans will profoundly enable drug development for the treatment of diabetic cardiomyopathy beyond blood glucose control.

Overall, a better comprehension of the mechanisms and clinical manifestations of diabetic cardiomyopathy will allow the development of more translatable and predictable preclinical models supporting target and drug discovery in academia and industry. The molecular taxonomy of diabetic cardiomyopathy to be developed will enable innovative and individualised treatment options for patients.

In terms of strengthening the competitiveness and industrial leadership in Europe the applicants could also include the relevant expertise from the small- and medium-sized enterprises (SMEs).Their involvement might offer a complementary perspective to industry and the academia, and help deliver the long-term impact of the project.

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