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

药物再利用可以填补有大量未得到满足的医疗需求的罕见疾病患者群体的一个重要空白。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，为更多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的神经、神经代谢和神经肌肉疾病的药物再利用。SIMPATHIC的主要加速创新是为具有不同基因诊断但神经症状和分子病理机制重叠的患者群体同时进行药物开发。SIMPATHIC加速药物再利用途径的主要成果包括：培养干细胞衍生的神经细胞模型的标准操作程序，该模型经证明与临床症状相关，并适用于高通量药物筛选；在先进的单芯片脑和3D脑器官模型中已证明有效的新药再利用候选方案，如与临床症状相关的分子生物标记物签名和细胞读数的逆转所证明的那样；设计创新的篮子临床试验，招募不同疾病的患者，利用和聚集个性化的临床终点；为患者和患者组织提供培训模块，使他们能够成为药物再利用途径的推动者；知识产权战略、商业模式、监管档案和患者准入战略的蓝图，由所有相关利益攸关方共同制定。SIMPATHIC同时开发多个适应症的再用途药物的概念验证将为以成本和时间高效的方式为罕见疾病患者群体开发个性化治疗机会指明前进道路。

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.