Development of a predictive biomarker for Parkinson's disease

帕金森病预测生物标志物的开发

• 批准号: MR/Y019415/1
• 负责人: George Tofaris
• 金额: $ 125.96万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY019415%2F1
• 关键词: Development; predictive; biomarker; Parkinson; disease

Parkinson's disease (PD) affects ~7 million people globally with a projected doubling in cases by 2040. Currently, the annual cost to the NHS is £2,118 per patient with an annual economic burden of £20,123 per PD household. There is no disease-modifying therapy currently, but such therapeutics are in clinical trials. A major bottleneck in the conduction of clinical trials is the identification of patients at the earliest stages of the pathogenesis and the exclusion of disease-mimics. PD starts several years before clinical presentation. Identifying individuals in this prodromal phase would be optimal for clinical trials and eventual instigation of disease-modifying therapies. We have developed a blood test that predicts PD pathology based on serum measurements of neuronally-derived alpha-synuclein, the key pathogenic protein in >95% of cases. Specifically, we immunocapture extracellular vesicles expressing the neuronal antigen L1CAM (L1EV) and have developed microfluidic prototypes for highly effective on-chip L1EV isolation within 30min. We discovered that total L1EV associated alpha-synuclein levels are increased in the prodromal and clinical phase of PD using >1,000 samples across multiple cohorts. We now seek support to develop this platform as a standardised clinical test. We will refine the assay parameters and translate our microfluidic prototype into a device suitable for clinical practice, to be used in conjunction with highly sensitive downstream marker quantification. The final assay format will be tested in a deeply phenotyped longitudinal cohort of individuals at risk of developing PD or patients with different rates of disease progression.

帕金森氏症（PD）影响全球约700万人，预计到2040年病例将翻一番。目前，NHS每年的费用为每位患者2118英镑，每个PD家庭每年的经济负担为20123英镑。目前还没有改善疾病的治疗方法，但这些治疗方法都处于临床试验阶段。进行临床试验的一个主要瓶颈是在发病机制的早期阶段识别患者并排除疾病模拟。PD在临床表现前几年就开始了。确定个体在这个前驱期将是最佳的临床试验和最终的疾病改善治疗的煽动。我们开发了一种血液检测方法，可以根据血清中神经元源性α -突触核蛋白的测定来预测帕金森病的病理，α -突触核蛋白是bbb95%病例的关键致病蛋白。具体来说，我们免疫捕获表达神经元抗原L1CAM （L1EV）的细胞外囊泡，并开发了微流控原型，用于在30分钟内高效地在芯片上分离L1EV。我们发现，在PD的前驱期和临床阶段，L1EV相关的α -突触核蛋白总水平升高。我们现在寻求支持，将这一平台发展为标准化的临床试验。我们将完善检测参数，并将我们的微流体原型转化为适合临床实践的设备，与高度敏感的下游标记物定量结合使用。最终的检测格式将在具有PD风险的个体或疾病进展速度不同的患者的深度表型纵向队列中进行测试。