I-Corps: Early Stage Diagnosis of Parkinson's Disease

这个I-Corps项目的更广泛的影响/商业潜力是提供帕金森病（PD）的生物学测量，这在确定PD患者的治疗策略和针对PD的药物开发方面非常有价值。PD是美国第二大常见的神经退行性疾病，2010年治疗费用超过144亿美元，预计到2040年将翻一番。PD的有效治疗需要可靠的PD早期诊断，但目前还没有明确诊断PD的客观测试。目前的诊断是基于外部症状，如震颤，缓慢的运动，僵硬的肌肉，脑成像，通常需要多次访问神经科专家，以避免误诊。事实上，2013年的一项研究确定，诊断一名新的PD患者的直接成本平均为7，322美元，美国每年有60，000名新的PD诊断，PD诊断市场估计至少为4亿美元。帕金森病（PD）早期诊断的新方法将对PD的预防和治疗产生巨大的影响，它将提供患者分层策略，并增加PD治疗临床试验的成功率。这个I-Corps项目是基于对蛋白质稳态在细胞中的作用的理解，并开发工具和技术来破译这些途径。PD是一种神经系统疾病，其主要特征是受影响的运动神经元中存在大量路易体沉积物，路易体是一种聚集蛋白质的混合物。文献报道已经鉴定了路易体中的某些生物标志物，其具有可以穿过血脑屏障的翻译后修饰的独特特征。该项目利用了识别PD血液样本中生物标志物特征的技术，并利用重组生成生物标志物并开发针对它们的抗体的工具，这将允许开发用于早期检测PD的非侵入性检测试剂盒。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

The broader impact/commercial potential of this I-Corps project is to provide a biological measure of Parkinsons disease (PD) which is extremely valuable in determining treatment strategies for PD patients and in drug development against PD. PD is the second most common neurodegenerative disease in the United States with treatment costs that exceeded $14.4 billion in 2010 and projected to double by 2040. Effective treatment of PD requires reliable early diagnosis of PD, however no objective test for definitive diagnosis of PD currently exists. Current diagnosis is based on outward symptoms like tremors, slow movement, rigid muscle, brain imaging and usually requires multiple visits with neurology specialists to avoid misdiagnosis. In fact, a 2013 study determined that the direct cost of diagnosis for a new PD patient on average amounts to $7,322 and with 60,000 new diagnosis of PD made every year in US, the market of PD diagnosis is estimated to be a minimum $0.4 billion. A new diagnostic approach for early stage of Parkinson's disease (PD) will have a tremendous impact on the prevention and treatment of PD by providing a stratification strategy of patients and increase the success in clinical trial of PD treatment. This I-Corps project is based on an understanding of the role of protein homeostasis in the cell and developing tools and techniques to decipher these pathways. PD is a neurological disease with the key hallmark of large deposits of Lewy bodies, an amalgam of aggregated proteins, in the affected motor neurons. Literature reports have identified certain biomarkers in Lewy bodies that have unique signature of post-translational modification which can cross the blood brain barrier. This project leverages techniques that identify signatures on the biomarker in PD blood samples and utilize tools that recombinantly generate biomarkers and develop antibodies against them, which will allow development of a test kit for early detection of PD non-invasively.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.