Plasma Assays for NPTX2 in Alzheimer's Disease

摘要 CogNext正在根据PAR-19-316提交这项建议，以开发新的诊断方法 阿尔茨海默病(AD)。广告是一个重大的医学挑战，也是失败的先例 淀粉样蛋白减少疗法的临床试验强调了对可以预测的生物标志物的需求 认知功能障碍的进展，并且在早期阶段就可以诊断和预测 疾病。CogNext诊断公司是由约翰·霍普金斯大学的神经科学家创立的，他的 记忆的细胞和分子基础研究证实脑脊液NPTX2是一个生物标志物 具有非凡的诊断性能。NPTX2在心脏生理学中起重要作用 阿尔茨海默病患者的脑组织和脑脊液中记忆能力明显下降。脑脊液NPTX2 与老年、非痴呆者的认知表现相关，区分对照 来自MCI以及A？或tau，增强了tau的诊断性能，并且在两个 独立研究预测MCI/早期AD的疾病进展。脑脊液中NPTX2的测定 已经获得专利保护，CogNext拥有独家许可的选择权。这里, CogNext寻求SBIR支持以测试一种新的检测方法的诊断性能 血浆中的NPTX2。该检测专门检测物理上与NPTX2接近的NPTX2 并为NPTX2依赖的脑生理学提供了一种新的指示物 将MCI/AD患者与年龄匹配的对照组区分开来。在Aim 1中，CogNext将工作 与生物技术合作伙伴一起测量存档生物标本中的血浆NPTX2，作为 淀粉样蛋白减少疗法的2期和3期临床试验。被选中的个人 3期试验被评估为先兆到早期发病的AD，并代表着未来 将寻求在阿尔茨海默病发作前开始治疗的临床试验。CogNext和 生物制药合作伙伴将确定血浆NPTX2是单独还是与广泛的 现有的测量方法包括脑脊液Aü、tau、PET-淀粉样蛋白和神经精神测试预测 进步。一种可以与脑脊液NPTX2诊断性能相匹配的血浆检测方法 改变临床试验设计的潜力。目标2将满足对高质量的需求 与NPTX2和共功能蛋白发生特异性反应的单抗 可以用来开发可商业化的分析方法。将使用以下方法生成兔单抗 脑脊液中NPTX2检测的B细胞筛选及特异性和实用性验证 和血浆。CogNext将以直接面向行业的方式与业务合作伙伴合作， 提供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.