Plasma Assays for NPTX2 in Alzheimer's Disease

阿尔茨海默病中 NPTX2 的血浆检测

• 批准号: 10325347
• 负责人: PAUL F WORLEY
• 金额: $ 50万
• 依托单位: COGNEXT DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10325347
• 关键词: Address; Affinity; Age; Alzheimer' s Disease; Alzheimer' s disease diagnostic; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Antibodies; Archives; Award; B-Lymphocytes; Binding; Biological Assay; Biological Markers; Biometry; Biotechnology; Brain; Businesses; Cerebrospinal Fluid; Clinical Data; Clinical Management; Clinical Trials; Clinical Trials Design; Cloning; Cognition; Cognitive; Collaborations; Complex; DNA Amplification Technics; DNA Ligation; Data; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Enrollment; Enzyme-Linked Immunosorbent Assay; Epitopes; Equilibrium; Failure; Future; Glutamate Receptor; Impaired cognition; Individual; Industry; Legal patent; Licensing; Ligation; Magnetic Resonance Imaging; Measures; Medical; Memory; Methods; Modeling; Molecular; Monoclonal Antibodies; Oryctolagus cuniculus; Performance; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Physiological; Physiology; Plasma; Plasma Cells; Play; Positron-Emission Tomography; Presenile Alzheimer Dementia; Process; Prognosis; Proteins; Publishing; Reagent; Recovery; Research; Research Personnel; Rodent; Role; Sampling; Small Business Innovation Research Grant; Specificity; Structure; Synapses; Technology; Testing; Time; Validation; Vendor; Work; aged; behavior test; biological specimen archives; cognitive performance; commercialization; follow-up; hippocampal pyramidal neuron; human subject; innovation; medical schools; mild cognitive impairment; non-demented; novel; novel diagnostics; predictive test; prognostic; prognostic performance; response; screening; tau Proteins; tau-1; therapeutic development

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.

抽象的 CogNext 正在提交此提案以响应 PAR-19-316，以开发新的诊断方法 阿尔茨海默病（AD）。 AD 代表了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凸显了对能够预测的生物标志物的需求 认知障碍的进展，并且在认知障碍的最早阶段具有诊断和预后作用 疾病。 CogNext Diagnostics 由约翰·霍普金斯大学的神经科学家创立， 记忆的细胞和分子基础研究确定 CSF NPTX2 是一种生物标志物 具有非凡的诊断性能。 NPTX2 在生理学中起着重要作用 患有 AD 的人类受试者的记忆力显着下降，并且大脑和脑脊液显着下降。脑脊液NPTX2 与老年、非痴呆个体的认知表现相关，区分对照 来自 MCI 以及 Aß 或 tau，增强了 tau 的诊断性能，并且有两种 独立研究预测 MCI/早期 AD 的疾病进展。 NPTX2 的 CSF 检测 已获得专利保护，CogNext 可以选择独家许可。这里， CogNext 寻求 SBIR 支持来测试新检测方法的诊断性能，该检测方法可检测 血浆中的 NPTX2。该测定专门检测物理上非常接近的 NPTX2 协同功能蛋白并提供了 NPTX2 依赖性脑生理学的新指标 将 MCI/AD 患者与年龄匹配的对照者区分开来。在目标 1 中，CogNext 将发挥作用 与生物技术合作伙伴一起测量存档生物样本中的血浆 NPTX2，作为 淀粉样蛋白减少疗法的 2 期和 3 期临床试验。入选的个人 第 3 阶段试验被评估为早发 AD 的前驱症状，并且代表了未来的情况 寻求在明显 AD 发作之前开始治疗的临床试验。 CogNext 和 Biopharm 合作伙伴将确定血浆 NPTX2 是单独使用还是与广泛的药物组合使用 现有的措施包括 CSF Aß、tau、PET-淀粉样蛋白和神经精神测试预测 进展。可以与 CSF NPTX2 的诊断性能相匹配的血浆检测 改变临床试验设计的潜力。目标 2 将满足高质量的需求 与 NPTX2 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检测方法。兔单克隆抗体将使用以下方法生成 最先进的 B 细胞选择，并验证了 CSF 中 NPTX2 检测的特异性和实用性 和血浆。 CogNext 将与业务合作伙伴以直接面向行业的方式合作， 提供最快的商业化途径和对 AD 研究的贡献。