Accelerating drug repurposing for rare neurological, neurometabolic and neuromuscular disorders by exploiting SIMilarities in clinical and molecular PATHology

利用临床和分子病理学的相似性，加速罕见神经系统、神经代谢和神经肌肉疾病的药物再利用

• 批准号: 10077172
• 金额: $ 6.43万
• 依托单位: EURO-ATAXIA
• 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=10077172
• 关键词: Accelerating; drug; repurposing; rare; neurological

Drug repurposing can fill an important gap for rare disease patient groups with large unmet medical needs. In comparison to traditional drug development, drug repurposing reduces the time and costs for drug development, regulatory approval, and market authorization. Yet, we need to increase the efficiency of the drug repurposing pathway to provide broader access to new therapeutic modalities for larger groups of patients. SIMPATHIC’s main objective is to accelerate drug repurposing for rare neurological, neurometabolic and neuromuscular disorders. SIMPATHIC’s main accelerating innovation is the simultaneous drug development for groups of patients with different genetic diagnoses but overlapping neurological symptoms and molecular pathomechanisms. SIMPATHIC’s key outputs accelerating the drug repurposing pathway include: Standard operating procedures for culturing stem cell-derived neuronal cell models with proven relevance for clinical symptoms and amenable to high-throughput drug screens; New drug repurposing candidates with proven efficacy in advanced brain-on-a-chip and 3D brain organoid models, as demonstrated by reversal of molecular biomarker signatures and cellular readouts associated with clinical symptoms; Designs of innovative basket clinical trials to which patients with different disorders are recruited, utilizing and aggregating personalized clinical endpoints; A training module for patients and patient organizations to empower them as drivers of the drug repurposing pathway; Blueprints for intellectual property strategies, business models, regulatory dossiers and patient access strategies, developed in co-creation between all relevant stakeholders. SIMPATHIC’s proof-of-concept for the simultaneous development of repurposed drugs for multiple indications will show the path forward to development of personalized treatment opportunities for groups of rare disease patients in a cost- and time-efficient manner.

药物再利用可以填补具有大量未满足医疗需求的罕见病患者群体的重要空白。与传统药物开发相比，药物再利用减少了药物开发、监管批准和市场授权的时间和成本。然而，我们需要提高药物再利用途径的效率，为更大的患者群体提供更广泛的新治疗方式。SIMPATHIC的主要目标是加速罕见神经系统、神经代谢和神经肌肉疾病的药物再利用。SIMPATHIC的主要加速创新是针对具有不同遗传诊断但重叠神经症状和分子病理机制的患者群体的同时药物开发。SIMPATHIC加速药物再利用途径的关键成果包括：培养干细胞衍生的神经元细胞模型的标准操作程序，该模型已被证明与临床症状相关，并适合高通量药物筛选;在先进的脑芯片和3D脑类器官模型中证明有效的新药再利用候选物，如通过与临床症状相关的分子生物标志物特征和细胞读数的逆转所证明的;设计创新的篮子临床试验，招募不同疾病的患者，利用和汇总个性化的临床终点;针对患者和患者组织的培训模块，使他们能够成为药物再利用途径的驱动者;知识产权战略、商业模式、监管档案和患者获取战略的蓝图，由所有相关利益相关者共同制定。SIMPATHIC同时开发用于多种适应症的再用途药物的概念验证将以具有成本效益和时间效益的方式为罕见病患者群体提供个性化治疗机会。