DOUBLE DOSE

2021

Cardiomyopathies, caused by genetic mutations affecting cardiac muscle components, pose significant economic and societal burdens due to their hereditary nature and early onset. Despite known genetic defects, predicting disease progression remains challenging due to extreme clinical variability. Recent research indicates that cardiomyopathy mutations induce metabolic stress, exacerbated by factors like obesity, which can accelerate disease progression. The Double Dose hypothesis suggests that targeting metabolic stress may offer preventive or curative strategies for these conditions.

The Focus
The Double Dose Consortium aims to understand how cardiomyopathy-causing mutations lead to structural changes in cardiomyocytes. This interdisciplinary effort combines experts in preclinical research, clinical genetics, health technology assessment, and clinical care focused on cardiomyopathy in both children and adults.

The Research
The consortium combines experts in preclinical research, clinical genetics, health technology assessment and clinical researchers with a strong clinical focus on cardiomyopathy in children and adults. These experts investigate how obesity and muscle adiposity contribute to vascular and cardiac muscle dysfunction in mutation carriers through the analysis of clinical data, patient samples, and experimental models. They will also study the mechanisms underlying ultrastructural changes in cardiomyocytes caused by these mutations, leading to impaired metabolism, contraction, relaxation defects, and disrupted cellular communication within the heart.

Utilizing extensive patient cohorts and ongoing studies, the consortium aims to optimize care for cardiomyopathy patients by assessing the cost-effectiveness of diagnostics and clinical interventions. They plan to translate findings on metabolic alterations into clinical trials targeting treatments that reduce metabolic stress. The Double Dose program will establish biobanks containing serum, tissue, and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to provide mechanistic insights into cardiomyopathy pathophysiology and improve diagnosis and care.

Origin
This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation, together with Stichting Hartedroom. The consortium is a continuation of the Dosis consortium, in which the interaction between mutation and external factors was investigated. They found that cardiomyopathy-mutations induce metabolic stress and that secondary metabolic stress, such as obesity accelerates disease progression.

 

Read More

Collaborators

Contact person:

Dr. J. van der Velden (Jolanda)

Principal investigators

Read more

National Network Healthy Living in a Healthy Environment

2022
Promoting a healthy lifestyle and maintaining it for a long time is crucial for the prevention of cardiovascular diseases. Lifestyle change areonly sustainable and impactful if it takes into account the context in which it occurs. The research Therefore, this netwerk will disseminate this insight widely to policymakers, researchers and everyone who contributes to promoting healthy behaviors. In this way, we can collectively achieve greater health gains when implementing potentially successful interventions. The ultimate goal is to achieve sustainable and impactful lifestyle change in the population. In the projects LIKE, BENEFIT and SUPREME NUDGE, unique expertise has been gained in the field of (1) embedding lifestyle interventions in complex systems, and (2) changing systems underlying lifestyle behavior. Within this national network, we want to disseminate and embed this expertise among researchers, practice professionals and policy makers. We will combine this expertise in the form of two toolboxes; a toolbox for practice professionals and policy makers and a toolbox for researchers. To this end, existing tools will be adapted, where necessary, to make them more widely usable. We aim to embed the toolboxes in (existing) structures and will make the toolboxes findable and disseminated through this netwerk. This network will serve as a structure for connections between stakeholders and contribute to the realization of a sustainable knowledge infrastructure. With this project we identify and create important conditions for successful further development and upscaling of innovative and sustainable ways to sustain healthy living for longer. With this we go further than many existing networks and knowledge infrastructures that focus only on 'effective interventions' but not on the structural embedding in systems or addressing the systems themselves. The origin From 2017, the Dutch Heart Foundation, together with ZonMw, invested in research by three healthy living consortia (LIKE, BENEFIT and SUPREME NUDGE). The common goal was to find new ways to achieve sustainable and impactful lifestyle change in the population. Heart Foundation and ZonMw asked the three healthy living consortia Supreme Nudge, LIKE and Benefit to join forces within this theme by using the knowledge they have gained over the past few years. Although the three consortia each had a different approach, the research leaders agreed on what is needed for lifestyle change to be truly successful: a shift in thinking about lifestyle change. Subsequently, the Dutch Heart Foundation and ZonMw provided follow-up funding to join forces and acquired knowledge in a new knowledge infrastructure.
Learn more

PREDICT 2

2019
Sudden cardiac arrest (SCA) remains a significant public health challenge, accounting for nearly 20% of all deaths in developed nations and approximately half of all heart disease-related fatalities. A notable subset of SCA cases occurs in individuals without prior heart disease diagnosis, resulting in profound psychosocial impacts on affected families and society. Ventricular fibrillation (VF) is the primary arrhythmia leading to SCA, often occurring outside healthcare settings with survival rates ranging from 5% to 20%. Prevention is crucial, yet gaps in our understanding of SCA causes and mechanisms hinder effective prevention efforts. Various genetic and non-genetic factors, such as gender, age, comorbidities, and lifestyle, likely influence SCA risk, but their specific contributions remain unclear. The Focus The PREDICT2 initiative brings together leading Principal Investigators with expertise in epidemiology, clinical studies, genetics, and functional research to elucidate factors contributing to SCA, uncover underlying mechanisms, and develop strategies for prevention and treatment. The Research Building on foundational work from PREDICT1, which involved extensive patient characterization and preclinical model development, PREDICT2 focuses on inherited arrhythmia syndromes as models to understand the arrhythmogenic substrate in more common cardiac syndromes associated with SCA. Specifically, PREDICT2 aims to: Identify genetic and non-genetic factors that contribute to SCA risk and develop personalized risk prediction algorithms for individual patient assessment. Conduct functional studies to elucidate the mechanisms underlying SCA, enabling the development of novel risk stratification and therapeutic approaches. Implement clinical studies to evaluate risk prediction algorithms and therapeutic interventions, aiming to enhance the treatment and prevention of SCA. Origin This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation.
Learn more
1 2 3 20

Looking for
Another item?

Back to overview
Newsletter
© 2024 Oscar Prent Assurantiën BV 
© 2025 | DCVA
Design & Bouw door: