Drug REpurposing with Artificial intelligence for Muscular disorderS

利用人工智能重新利用药物治疗肌肉疾病

• 批准号: 10084070
• 金额: $ 91.46万
• 依托单位: SAMSARA THERAPEUTICS LTD
• 依托单位国家: 英国
• 项目类别: EU-Funded
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10084070
• 关键词: Drug; REpurposing; Artificial; intelligence; Muscular

According to World Health Organization, to date, fewer than 6% of rare diseases (RDs) have an approved treatment option. In the light of this observation, it appears crucial to develop disruptive approaches that allow to find treatments for multiple RDs. To achieve this goal, DREAMS will start from 5 rare neuromuscular disorders (NMD) that share common pathophysiological characteristics related to dysfunctions of autophagy and desmin disorganization. Using skeletal muscle cells derived from induced pluripotent stem cells (skMC iPSC), DREAMS will i) identify shared biomarkers of the 5 diseases and ii) perform a high throughput drug screen on all 5 diseases. Through a first Artificial Intelligence (AI) based solution, the output of the drug screening will be used to find drug targetsshared between the diseases. A second AI based solution will be used to find drug candidates (repurposable drugs and new molecular entities) for these shared drug targets. A third AI-based solution will be used to find additional diseasesthat could be treated through the shared drug targets, in order to extend the indications for the most promising drug candidates. Following their discoveries, the promising drug candidates will be tested for efficacy and safety in both iPSC and mouse models of the 5 NMDs and additional diseases. In parallel, DREAMS will design an adaptive clinical trial to prepare the final stages of drug development of these novel drug candidates with multiple indications. Together, these technological and conceptual innovations will allow the DREAMS consortium to i) develop therapies to treat multiple NMDs and related diseases, ii) to create a novel clinical design that generates a regulatory pathway for drugs that treat heterogeneous groups of patients suffering from RDs iii) to further the scientific understanding of commonalities in RDs, and iv) to create a reusable drug development platform to discover safe and effective treatments for RDs in general.

根据世界卫生组织的数据，迄今为止，只有不到6%的罕见病（rd）有批准的治疗方案。根据这一观察结果，似乎至关重要的是开发能够找到多种rd治疗方法的破坏性方法。为了实现这一目标，DREAMS将从5种罕见的神经肌肉疾病（NMD）开始，这些疾病具有与自噬功能障碍和desmin紊乱相关的共同病理生理特征。利用诱导多能干细胞（skMC iPSC）衍生的骨骼肌细胞，DREAMS将i)鉴定5种疾病的共同生物标志物，ii)对所有5种疾病进行高通量药物筛选。通过第一个基于人工智能（AI）的解决方案，药物筛选的输出将用于寻找疾病之间共享的药物靶点。第二个基于人工智能的解决方案将用于为这些共享的药物靶点寻找候选药物（可重复使用的药物和新的分子实体）。第三种基于人工智能的解决方案将用于发现可通过共享药物靶点治疗的其他疾病，以扩大最有希望的候选药物的适应症。在他们的发现之后，有希望的候选药物将在iPSC和5种nmd和其他疾病的小鼠模型中进行有效性和安全性测试。同时，DREAMS将设计一项适应性临床试验，为这些具有多种适应症的新型候选药物的药物开发的最后阶段做准备。总之，这些技术和概念创新将使DREAMS联盟能够i)开发治疗多种nmd和相关疾病的疗法，ii)创建一种新的临床设计，为治疗异种RDs患者群体的药物产生监管途径，iii)进一步科学地了解RDs的共性，iv)创建一个可重复使用的药物开发平台，以发现安全有效的一般RDs治疗方法。