Phaedra-impact

In preceding decades, conventional therapies have notably enhanced the survival rates of heart failure (HF) patients. However, a subset of individuals, particularly younger patients afflicted with dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM), still confront disease progression despite these treatments. This underscores the necessity for innovative approaches. The ARENA-PRIME initiative aims to address this gap by focusing on the development of novel gene therapies tailored to the specific disease mechanisms underlying DCM, attributed to mutations in the RBM20 and LMNA genes, as well as ACM, and associated with mutations in the DSGL2 and PKP2 genes. The goal is to progress towards first-in-human clinical trials, particularly focusing on LMNA disease, and to establish preclinical proof-of-concept for ACM therapies targeting DSGL2 and PKP2. The Research The ARENA-PRIME researchers utilize insights from previous programmes on cardiac gene therapies (e.g., inhibitory RNAs such as allele-specific short hairpin RNAs, antimiRs, etc.) and gene editing technologies (e.g., base- and prime editing) to develop novel treatments for dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). This effort is supplemented by advanced research on adeno-associated viral vectors and the integration of heart tissue collections with cutting-edge sequencing technologies (like single-cell sequencing) to further explore disease mechanisms. At the beginning of the ARENA-PRIME programme, a (end-) user committee has been established, making sure that (end-)users are  closely involved in the design of the studies and the implementation of the co-created studies and deliverables. This committee meets annually alongside the program's research meetings to provide guidance to investigators on optimizing the program's outcomes for (end-) users. It addresses all feedback, inquiries, and recommendations, whether requested or spontaneous. This committee meets once per year in conjunction with the programme’s research meetings and advises the investigators about the course of the programme and what actions need to be taken in order to maximise the probability that the (end-) users will be able to utilize and/or benefit from the results. This committee addresses any comments, remarks, questions and advice they may have, solicited or otherwise. The members of the ARENA-PRIME user committee include cardiomyopathy patients and their relatives, clinicians (e.g. cardiologists), representatives from related research programs (e.g., RegMedXB, H2020-TRAIN-HEART), and industry stakeholders including biotech and pharma company representatives and venture capitalists. Supporting Young Investigators The programme prioritizes attracting and nurturing young talent, providing hands-on training and fellowship awards to facilitate their career development. Over 20 young investigators participate, benefiting from exposure to collaborative research environments. To further support this career development, five fellowship awards of 50.000€ have been granted the past three years to junior postdoctoral researchers in the laboratories of the Hubrecht Institute, University Medical Center Utrecht, Amsterdam UMC (location VUmc and AMC) and Maastricht University. Origin The former CVON-ARENA programme (2012-2017) advanced understanding of cardiac RNA species in heart failure (microRNAs, lncRNAs and circular RNAs). The CVON-ARENA programme (2012-2017) advanced understanding of cardiac RNA species, such as microRNAs, lncRNAs, and circular RNAs, in various forms of heart failure (HF). This subsequent ARENA-PRIME programme (2018-2023), funded by the Dutch Heart Foundation, targets treatment-resistant HF forms, particularly in younger patients with dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM). In 2023 ARIME-PRIME received a matching grant from the Dutch Heart Foundation to work on their research together with a private partners, so that they can achieve their ambitions and objectives more quickly.

Cardiovascular disease (CVD) is the leading global cause of mortality and morbidity, with ischemic heart disease (IHD) representing approximately half of all CVD-related deaths. Precise, personalized risk assessment and treatment recommendations are crucial for addressing the diverse population at risk of CVD. Current standard approaches rely on algorithms that incorporate a limited set of traditional risk factors to estimate CVD and IHD risk. However, significant cardiovascular events often occur in individuals categorized as low risk, underscoring the need for ongoing research to enhance preventive strategies. The Focus The MyDigiTwin initiative aims to provide individuals with personalized insights into their cardiac health, enabling proactive monitoring and management of cardiovascular conditions. This integrated digital health platform empowers individuals to take control of their cardiac health by offering accessible, data-driven insights and tools. The Research MyDigiTwin is a pioneering research initiative focused on revolutionizing cardiac health management by integrating advanced AI technologies with extensive patient data. The development of MyDigiTwin involves harnessing large-scale longitudinal datasets from over 500,000 patients, combined with sophisticated AI algorithms. This approach enables the platform to analyze diverse health parameters and generate tailored recommendations for users based on their unique health profiles. By leveraging AI and comprehensive patient data, MyDigiTwin represents an innovative approach to preventive and personalized healthcare, facilitating early detection and intervention for cardiovascular conditions. Origin This project was funded within the Big Data & Health Program. The focus of this public-private research program is the use of big data for the early detection and prevention of cardiovascular diseases. The program has been developed by NWO, ZonMw, the Dutch Heart Foundation, the Top Sectors Life Sciences & Health (LSH), ICT and Creative Industry, the Ministry of Health, Welfare and Sport, and the Netherlands eScience Center. Within this research program, the ambitions of the Dutch Heart Foundation, the Ministry of Health, Welfare and Sport, and the Netherlands eScience Center were aligned with the ambitions of Commit2Data for the Top Sectors ICT, LSH, and Creative Industry, as described in the 2018-2019 Kennis- en Innovatiecontracts between NWO and the Top Sectors.