GEREMY_Gene Therapy for treatment of rare inherited Arrhythmogenic Cardiomyopathy

开发一种治疗罕见心脏病的方法是一个冒险、昂贵和耗时的过程，这一过程受到对这些疾病的病理生理机制的了解不足和缺乏相关疾病模型的阻碍。Geremy联盟建议通过开发一种针对致病PLN(非桥粒)和PKP2(心脏桥粒)突变的遗传性心律失常致心肌病(ACM)的基因疗法(GT)来克服这一挑战。Geremy财团将应用一种独特的并行方法，并研究各种有前景的GT方法(寡核苷酸化学、基因编辑和基因传递)。此外，该联盟将设计疾病模型，以适当评估治疗干预措施，并旨在为GT提供体外和体内的临床前概念证明。与目前的技术相比，GT的一个重大好处是，GT具有成为罕见心脏病的根治药物的潜力。基于之前的成功，Geremy将把PLN和PKP2作为该技术的路线图。修复导致疾病的PLN和PKP2基因的主要缺陷将导致保持甚至恢复心肌的收缩能力。通过这种方法，Geremy将致力于治疗遗传性ACM和可能的其他心肌病，从而显著减轻医疗负担。该项目的临床前研究和心脏遗传学专家将为突变纠正提供临床前有效性和安全性数据。拥有监管和临床试验专业知识的合作伙伴(EXOM、EUF、NLHI)将准备在项目完成后立即开始临床试验，并申请孤儿药物指定。患者组织和KUL伦理合作伙伴EUPATI将确保该项目持续与患者需求和伦理观点保持一致。整个联盟将致力于传播和传播成果，以确保最大限度地利用这项突破性技术。

Development of a cure for rare cardiac diseases is a risky, costly and time-consuming process, which is hampered by insufficient insight into pathophysiological mechanisms of the diseases and lack of relevant disease models. The GEREMY consortium proposes to overcome this challenge by developing a gene therapy (GT) for inherited arrhythmogenic cardiomyopathy (ACM), by targeting the disease-causing PLN (non-desmosomes) and PKP2 (cardiac desmosomes) mutations. The GEREMY consortium will apply a unique parallel approach and investigate various promising GT approaches (oligonucleotide chemistries, gene editing and gene delivery). Also, the consortium will engineer disease models for proper assessment of therapeutic interventions and aims to provide in vitro & in vivo preclinical proof of-concept for the GT. A significant benefit compared to current technologies is that the GT has the potential to be a curative treatment for rare cardiac diseases. Based on previous successes, GEREMY will target PLN & PKP2 as a roadmap of the technology. Restoring the primary defect in the PLN & PKP2 genesthat cause the disease will lead to preserving or even restoring myocardial contractility. Through this approach, GEREMY will work towards a curative treatment of inherited ACM and likely other cardiomyopathies, which significantly reduces the healthcare burden. The project’s experts in preclinical research and cardiac genetics will deliver preclinical efficacy and safety data for the mutation correction. The partners with regulatory and clinical trial expertise (EXOM, EUF, NLHI) will prepare for immediate start of clinical trials upon project completion, and apply for orphan drug designation. EUPATI, a patient organisation and KUL ethics partner will ensure that the project is continuously aligned with patient needs and ethical perspectives. The whole consortium will contribute to communicate an disseminate the results to ensure maximum exploitation of this breakthrough technology.