Genetically diverse mini-heart models for stratified cardiotoxicity prediction.

用于分层心脏毒性预测的遗传多样性迷你心脏模型。

• 批准号: 10026262
• 金额: $ 56.24万
• 依托单位: CYTOCHROMA LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=10026262
• 关键词: Genetically; diverse; mini; heart; models

Unexpected cardiac adverse effects and lack of testing in distinct genetic backgrounds are the leading causes of clinical trial discontinuation, the withdrawal of drugs from the market and post-approval withdrawal of medicines.VISIONThis project aims to deliver physiologically relevant multicellular cardiac models from a diverse genetic background to more accurately predict the safety and effect of new drugs in a global population. Cytochroma is a pioneering biotechnology company that supplies the pharmaceutical industry with ethnically diverse models for drug discovery and development. FOCUS To provide robust, reliable and scalable models that are cost effective, viable alternatives to the current gold standard to provide more accurate testing and capture a large market share.PLANCytochroma will utilise its expertise in developing 3D iPSC derived models and work with the Medicines Discovery Catapult, to exploit their access to industry contacts, expertise and state-of-the-art equipment. Together we will develop these models from proof of concept through to scale up for commercial manufacture.1. Cytochroma will produce genetically diverse models containing multiple cardiac lineage cells.2. The MDC and Cytochroma will characterise these models and conduct independent testing to validate the models.3. To qualify the multicellular models for use by industry, a range of cardiotoxins will be evaluated and cell manufacture translated to automated systems for large scale manufacture.4. Post-project these models will be supplied to MDC partners such as Astrazeneca and Merck for commercial validation and feedback.OBJECTIVES1. Identification of a method to generate functional cardiac models2. Externally validate models in response to known cardio-toxins.3. Scale production and identify optimal methods of transport.INNOVATIONLineage specific cardiotoxic models and responses have been reported in simple 2D configurations, (Burnett 2019, Grimm 2018) however, access to multicellular 3D cardiac models from different backgrounds is a global first. OUTCOMES * Accelerated drug development* Preventing late stage clinical drug failure* Providing stratified healthcareWe seek a revolution in preclinical testing and substantial improvements in the efficiency of new drug development and are sourcing public and private funding to develop translational science and technologies that provide substantial social, economic and environmental impact. With a regulatory drive to eliminate animal testing by 2035, pharmaceutical industry is investing in iPSC models and technology. Cytochroma is well placed to take advantage of this emerging and profitable market.

意外的心脏不良反应和缺乏不同遗传背景的测试是导致临床试验中止、药物从市场撤回和批准后药物撤回的主要原因。VISION该项目旨在提供来自不同遗传背景的生理相关的多细胞心脏模型，以更准确地预测新药在全球人群中的安全性和效果。Cytochroma是一家开创性的生物技术公司，为制药行业提供不同种族的药物发现和开发模式。专注于提供强大、可靠和可扩展的模型，这些模型是当前黄金标准的成本效益和可行的替代品，以提供更准确的测试并占领更大的市场份额。PLANCytochroma将利用其在开发3D iPSC衍生模型方面的专业知识，并与Medicines Discovery Catapult合作，利用其获得行业联系、专业知识和最先进设备的机会。我们将共同开发这些模型，从概念验证到商业规模的扩大。Cytochroma将产生包含多个心脏谱系细胞的遗传多样性模型。MDC和Cytochroma将对这些模型进行验证，并进行独立测试以验证模型。为了使多细胞模型有资格用于工业，将评估一系列心脏毒素，并将细胞制造转化为自动化系统用于大规模生产。项目后，这些模型将提供给MDC合作伙伴，如阿斯利康和默克进行商业验证和反馈。识别生成功能性心脏模型的方法2.外部验证模型对已知心脏毒素的反应。INNOVATIONLineage特异性心脏毒性模型和反应已经在简单的2D配置中报道过（Burnett 2019，Grimm 2018），然而，从不同背景获得多细胞3D心脏模型是全球首次。成果 * 加速药物开发 * 预防晚期临床药物失败 * 提供分层医疗我们寻求临床前测试的革命和新药开发效率的实质性提高，并正在寻求公共和私人资金来开发转化科学和技术，提供重大的社会，经济和环境影响。随着监管机构要求到2035年消除动物试验，制药行业正在投资iPSC模型和技术。Cytochroma处于有利地位，可以利用这个新兴且有利可图的市场。