Plasma Assays for NPTX2 in Alzheimer's Disease

摘要 CogNext正在提交这项提案，以响应PAR-19-316，开发新的诊断方法， 阿尔茨海默病（AD）。AD代表了一个重大的医学挑战和失败的先例 淀粉样蛋白减少疗法的临床试验强调了对生物标志物的需求， 认知障碍的进展，并且在认知障碍的最早阶段是诊断和预后的。 疾病CogNext Diagnostics是由来自约翰霍普金斯的神经科学家创立的， 对记忆的细胞和分子基础的研究将CSF NPTX 2鉴定为生物标志物， 具有非凡的诊断性能NPTX 2在神经元的生理学中起着重要的作用。 在患有AD的人类受试者的脑和CSF中，CSF NPTX 2 与老年非痴呆个体的认知表现相关， 从MCI以及Ablad 3或tau，增强tau的诊断性能，并在两个 独立研究预测MCI/早期AD的疾病进展。NPTX 2的CSF测定 已获得专利保护，CogNext可以选择独家许可。在这里， CogNext寻求SBIR支持，以测试一种新检测方法的诊断性能， 血浆中的NPTX 2。该检测试剂盒特异性检测NPTX 2，该NPTX 2与 共功能蛋白质，并提供了NPTX 2依赖性脑生理学的新指标， 将MCI/AD个体与年龄匹配的对照区分开来。在目标1中，CogNext将起作用 与生物技术合作伙伴一起测量作为以下研究的一部分收集的存档生物标本中的血浆NPTX 2 淀粉样蛋白减少疗法的2期和3期临床试验。被选入 3期试验被评估为前驱期至早发性AD， 临床试验将寻求在显性AD发作前开始治疗。CogNext和 Biopharm合作伙伴将确定血浆NPTX 2单独或与广泛的 现有的措施，包括CSF Ablation，tau，PET淀粉样蛋白，和神经精神病测试预测 进展可以匹配CSF NPTX 2的诊断性能的血浆测定具有 改变临床试验设计的潜力。目标2将解决高质量的需求 与NPTX 2和共功能蛋白特异性反应的单克隆抗体（mAb）， 可用于开发可商业化的分析。将使用以下方法生成兔mAb： 最先进的B细胞选择，并验证了CSF中NPTX 2测定的特异性和实用性 和血浆。CogNext将以直接面向行业的方式与商业伙伴合作， 提供了最快的商业化途径和对AD研究的贡献。

Abstract CogNext is submitting this proposal in response to PAR-19-316 to develop novel diagnostics for Alzheimer’s disease (AD). AD represents a major medical challenge and precedent from failed clinical trials with amyloid reducing therapies highlights the need for biomarkers that can predict progression of cognitive failure, and that are diagnostic and prognostic at the earliest stage of disease. CogNext Diagnostics was founded by neuroscientists from Johns Hopkins whose studies of the cellular and molecular basis of memory identified CSF NPTX2 to be a biomarker with extraordinary diagnostic performance. NPTX2 plays an essential role in the physiology of memory and is markedly decreased in brain and CSF of human subjects with AD. CSF NPTX2 correlates with cognitive performance in aged, non-demented individuals, distinguishes controls from MCI as well as Aß or tau, enhances the diagnostic performance of tau, and in two independent studies predicts progression of disease in MCI/early AD. A CSF assay for NPTX2 has been awarded patent protection and CogNext has an option for exclusive license. Here, CogNext seeks SBIR support to test the diagnostic performance of a new assay that detects NPTX2 in plasma. The assay specifically detects NPTX2 that is in close physical proximity to co-functional proteins and provides a novel indicator of NPTX2-dependent brain physiology that distinguishes individuals with MCI/AD from age-matched controls. In Aim 1, CogNext will work with a biotech partner to measure plasma NPTX2 in archived biospecimens collected as part of phase 2 and phase 3 clinical trials of an amyloid reducing therapy. Individuals selected for the phase 3 trail were assessed to be prodromal to early onset AD and are representative of future clinical trials that will seek to start therapy before the onset of manifest AD. CogNext and Biopharm partner will determine if plasma NPTX2 alone or in combination with extensive existing measures including CSF Aß, tau, PET-amyloid, and neuropsychiatic testing predicts progression. A plasma assay that could match the diagnostic performance of CSF NPTX2 has the potential to transform clinical trial design. Aim 2 will address the need for high quality monoclonal antibodies (mAbs) that specifically react with NPTX2 and co-functional proteins and that can be used to develop commercializable assays. Rabbit mAbs will be generated using state of the art B-cell selection and validated for specificity and utility for NPTX2 assays in CSF and plasma. CogNext will work with business partners in a direct-to-industry approach that offers that fastest path to commercialization and contribution to AD research.