Cardiovascular Moonshot (RegMed XB)

2018

Heart failure is a global public health issue with a largely equal distribution between men and women. For patients with end-stage heart failure limited treatment options are available. The Cardiovascular Moonshot of RegMed-XB (CMRM-XB) is a comprehensive program based on the concept of developing personalized cardiac regenerative therapies tailored to individual patients. The researchers aim to enhance the body's inherent regenerative capacity, such as improving contractility and perfusion of the heart muscle, repairing or replacing coronary arteries and heart valves. Importantly, researchers will gain insights into optimizing heart treatment and potentially preventing certain cardiovascular diseases in patients.

The Research
The research is focused on the creation of a(n) (additional) solution(s) for patients by regenerating the human heart inside (in-situ) or outside of the body (ex-situ). Repair of the heart in a cardiac perfusion bioreactor (ex-situ) offers unique opportunities, including the possibility to apply treatments without off-target effects to distant organs or wash-out of therapeutics. Initially, this could be an option to restore donor hearts for transplant recipients. After restoring the heart, it will be re-implanted. This strategy also facilitates exploration of gene therapy for hereditary diseases. Along this process, the researchers learn how to treat the heart better and eventually also aim to deduce how to treat the heart inside a patient.

The Cardiovascular Moonshot of RegMed XB is the most recent addition to the Moonshot initiatives. To date, it has completed a hypothermic pilot study that has enhanced researchers' expertise in perfusion models. Currently, this model is undergoing further refinement for optimal heart preservation. Additionally, ongoing histopathological analysis of heart valves aims to elucidate how these valves remodel in response to altered fluid dynamics within the ex vivo heart platform.

The cardiovascular Moonshot consists of a multidisciplinary team of transplant surgeons (Utrecht), cardiologists (Utrecht, Maastricht), engineers (Eindhoven) and biologists (Leiden) with the support and input of key stakeholders including patients and companies.

The origin

RegMed XB is a virtual institute that currently comprises Dutch and Belgian public (universities and governments) and private (health foundations and companies) partners that work together to develop regenerative medicine solutions. Regenerative medicine aims to restore degenerated, diseased, or damaged tissues and organs, thereby increasing vital functioning and reducing the cost of healthcare. RegMed XB collaborates on ambitious projects in the field of regenerative medicine. Initially, five health foundations have joined the TKI-program by Health~Holland to define the research objectives and co-govern the projects. Numerous companies have joined and the regional governments support both the research and its valorisation.

The cardiovascular Moonshot recently received follow-up funding from the Dutch Heart Foundation through the Open PSS program, which the Dutch Heart Foundation receives from Health~Holland. In addition, companies involved are also making a financial contribution; these are Coagulation Profile and Axion Biosystems.

Contact person:

Prof. Dr. P. Doevendans (Pieter)

p.doevendans@umcutrecht.nl

Principal investigators

Prof. Dr. P. Doevendans (Pieter)

p.doevendans@umcutrecht.nl

Prof. Dr. C.V.C. Bouten (Carlijn)

c.v.c.bouten@tue.nl

Prof. Dr. M. Goumans (Marie-José)

m.j.goumans@lumc.nl

Dr. B.M.E. Mees (Barend)

barend.mees@mumc.nl

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The IN-CONTROL II consortium builds upon the success of IN-CONTROL I, which highlighted the pivotal role of the microbiome in low-grade inflammation associated with atherosclerotic cardiovascular diseases (CVD) and related risk factors such as lipid levels and microbiome-derived metabolites. These insights are crucial for addressing the rising rates of CVD-related mortality, particularly in aging and overweight populations.
The Focus
The objectives of IN-CONTROL II are to:

Investigate the mechanisms underlying trained immunity in CVD patients, considering factors like senescence, age, sex, and obesity.
Elucidate the interactions between microbiome-derived signals (aromatic amino acids, metabolites, bile acids) and immune senescence in obesity-related cardio-metabolic diseases.
Identify novel therapeutic targets and develop pharmacological and microbiome-based therapies to counteract inappropriate induction of trained immunity and inflammation in cardiovascular disease.

The Research
The consortium aims to shift from association to causality, from population-based cohorts to patient groups with atherosclerotic cardiovascular disease (CVD) and from observation to intervention. In this transition, it will also take advantage of recent developments in the network of the consortium, delineating cellular senescence as a druggable target for the broad spectrum of age-related chronic diseases, including cardiovascular diseases, and identification of components of the bile acid-signaling system for this purpose. Another recent development of the recognition of innate immune memory (‘trained immunity’) as pathophysiological mechanism in atherosclerotic CVD.
The consortium will conduct proof-of-principle trials in specific patient cohorts, employing advanced experimental techniques such as systems biology, single cell sequencing, innovative animal models, and metabolic flux quantification (fluxomics). A talent program will facilitate knowledge transfer and skill development for young researchers within the consortium, emphasizing rapid translation of research findings into clinical applications.
Origin
This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation.

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ADMINISTER II

2024

Heart failure is an escalating global health challenge, affecting over 64 million people worldwide. Despite advancements in guideline-directed medical therapy (GDMT) that significantly reduce mortality and hospitalizations, many patients still do not receive optimal medication regimens or dosages. This gap in care highlights the need for innovative, collaborative approaches to improve treatment delivery and outcomes.
The research
The ADMINISTER I study demonstrated the potential of digital care solutions to enhance medication prescription accuracy and accelerate the time required to achieve GDMT. In real-world clinical practice, optimizing medications to meet GDMT standards is a complex and time-intensive process. It requires frequent monitoring, adjustments, and multiple visits to healthcare providers, posing a significant burden on both patients and clinicians.
Building on this foundation, the ADMINISTER II consortium is a collaborative effort uniting multiple stakeholders, including healthcare providers, researchers, and (biomedical) engineers. This consortium aims to evaluate the impact of a cutting-edge digital care intervention designed to streamline medication optimization. By leveraging a robust remote monitoring infrastructure, this approach seeks to make the process more efficient, scalable, and accessible, while focusing on improving critical clinical outcomes.
This collaborative digital intervention represents a transformative step toward patient care and offers hope for better heart failure management. Insights from ADMINISTER II could pave the way for the widespread adoption of innovative, integrated solutions, benefiting patients, caregivers, and healthcare systems worldwide.
The ADMINISTER II consortium brings together the expertise of a leading Technical University, major referral hospitals, and a renowned academic center to deliver state-of-the-art digital care across a large nationwide hospital network. This unique synergy is pivotal to achieving the ambitious goals set by the Dutch Cardiovascular Alliance (DCVA): a 25% reduction in the cardiovascular burden by 2030.
By integrating cutting-edge digital infrastructure with clinical excellence, the consortium aims to significantly lower hospitalizations and mortality rates. This partnership not only accelerates the adoption of innovative digital solutions but also ensures their effective implementation in diverse healthcare settings, marking a critical step toward transforming cardiovascular care on a national scale.
The origin
The ADMINISTER II is created after successful completion of the ADMINISTER I trial.
The ADMINISTER I was fully funded by Amsterdam UMC and was a collaboration with Netherlands heart institute, UMC Utrecht, Rode Kruis hospital and CCN.
The ADMINISTER II consortium will be on a larger scale; with a larger network and multiple funders.

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