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是针对Par-19-316提交的，以开发新颖的诊断。 阿尔茨海默氏病（AD）。广告代表了一个重大的医疗挑战，并且是失败的先例 淀粉样蛋白还原疗法的临床试验突出了对可以预测的生物标志物的需求 认知失败的进展，并且在最早的阶段诊断和预后是 疾病。 Cognext Diagnostics是由Johns Hopkins的神经科学家创立的 记忆的细胞和分子基础的研究确定CSF NPTX2是生物标志物 具有非凡的诊断性能。 NPTX2在生理学中起着至关重要的作用 记忆力，在人类受试者的大脑和CSF中明显减少AD。 CSF NPTX2 与老年非痴呆个体的认知表现相关，可区分控制 从MCI以及Aß或TAU，可以提高Tau的诊断性能 独立研究预测MCI/早期AD中疾病的进展。 NPTX2的CSF分析 已获得专利保护，Cognext可以选择独家许可证。这里， Cognext寻求SBIR支持，以测试一种新测定的诊断性能 NPTX2在等离子体中。该测定专门检测NPTX2，该NPTX2与 共同功能蛋白，并提供了NPTX2依赖性脑生理学的新指标 从年龄匹配的对照组中具有MCI/AD的独特个人。在AIM 1中，Cognext将起作用 与生物技术合作伙伴一起测量收集的存档生物测量中的血浆NPTX2作为一部分 淀粉样还原疗法的2阶段和3阶段临床试验。被选为 评估了第3阶段的步道是前瞻到早期AD的前瞻性，并且代表了未来 临床试验将试图在明显广告发作之前开始治疗。 cognext和 Biopharm合作伙伴将确定血浆NPTX2是单独的还是与广泛的 现有措施包括CSFAß，TAU，PET淀粉样蛋白和神经心理测试预测 进展。可以与CSF NPTX2的诊断性能相匹配的血浆测定 改变临床试验设计的潜力。 AIM 2将满足高质量的需求 单克隆抗体（mAb），该抗体特异性与NPTX2和共同功能蛋白以及 可以用来开发可商业化的测定法。兔子mab将使用 最先进的B细胞选择，并在CSF中针对NPTX2分析的特异性和实用性进行了验证 和等离子体。 Cognext将与业务合作伙伴一起以直接到行业的方法合作 为商业化和对广告研究的贡献提供了最快的途径。