Development of an ophthalmic diagnostic probe for cerebral amyloid angiopathy in patients

开发用于患者脑淀粉样血管病的眼科诊断探针

• 批准号: 10515850
• 负责人: Stella Sarraf
• 金额: $ 144.28万
• 依托单位: AMYDIS DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10515850
• 关键词: Address; Advanced Development; Age; Age-associated memory impairment; Alzheimer' s disease patient; Amyloid; Amyloid beta-Protein; Amyloidosis; Animal Model; Arteries; Autopsy; Award; Binding; Biological Markers; Biopsy; Blood Vessels; Boston; Brain; Brain hemorrhage; Capital; Caring; Cerebral Amyloid Angiopathy; Cerebral hemisphere hemorrhage; Cerebrum; Clinical; Clinical Trials; Collaborations; Complement; Data; Databases; Deposition; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Dose; Drug Kinetics; Drug Prescriptions; Early Diagnosis; Elderly; Equipment; Eye; Fluorescence; Fluorescent Probes; Formulation; Generations; Goals; Guidelines; Hemorrhage; Histopathology; Human; Imaging Techniques; In Vitro; Individual; Intravenous; Iowa; Kilogram; Laboratories; Lead; Magnetic Resonance Imaging; Methods; Mission; Ophthalmologist; Outcome; Patient Care; Patients; Peptides; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Physicians; Plasma; Procedures; Production; Property; Reporting; Research; Retina; Risk; Safety; Secure; Series; Specialist; Stroke; Symptoms; Testing; Tissues; Toxicology; Transgenic Mice; Universities; Work; abeta deposition; authority; cohort; commercialization; cost; cost effective; crystallinity; design; diagnosis standard; disease diagnosis; fluorescence imaging; high risk; improved; in vivo; instrument; meetings; mouse model; novel; pre-clinical; preclinical study; programs; response; retinal imaging; scale up; screening; small molecule; stability testing; standard care; stroke risk; stroke-like outcome; tool

Project Summary Cerebral amyloid angiopathy (CAA) is a common neuropathological finding among older adults and is characterized by amyloid beta (Aβ) deposits in blood vessel walls of the brain. CAA is a major cause of spontaneous intracerebral hemorrhage and is an important contributor to age related cognitive decline. Diagnosis is often missed by physicians as the presenting symptoms are similar to a stroke and can be further complicated as CAA is found in over 80% of Alzheimer's disease patients. Standard diagnosis of probable CAA involves expensive imaging techniques and an invasive brain biopsy. The only definitive way to diagnose CAA is through post-mortem analysis. An antemortem diagnostic is needed that can reliably identify CAA at the early, asymptomatic stages, enabling a correct diagnosis to avoid medications contraindicated in the disease, which can increase the individual's stroke risk. Furthermore, a useful and affordable outcome marker is needed for clinical trials focused on therapies for CAA that could stop or reverse the progression of the disease. Amydis aims to address these unmet needs by identifying A in the eye, as a window to the brain, for early detection of CAA. Amydis is meeting this need with the development of a novel retinal diagnostic probe. Our novel retinal diagnostic probe, AMDX-2011P, has fluorescent properties amenable for use with standard retinal imaging equipment found in the ophthalmologists' office and fluoresces at a wavelength suitable for use with conventional instruments, it penetrates the retina when administered systemically at significant concentrations, is non-toxic in preclinical animal models, and has crystalline properties that allow for consistent large-scale manufacturing. In this proposal, Amydis will manufacture AMDX-2011P under GMP guidelines, formulate AMDX-2011P for i.v. delivery, test stability, and then undertake a phase 1 clinical trial with single ascending doses in healthy subjects (N=24) and then test the optimal dose in a small cohort of CAA patients (N=5). Completion of these aims will advance the development of our in vivo ocular diagnostic test, getting us one step closer to our mission of providing an antemortem, simple, and affordable CAA diagnostic.

项目摘要 脑淀粉样血管病(CAA)是老年人常见的神经病理改变。 以脑血管壁中的淀粉样β蛋白(Aβ)沉积为特征。CAA是导致 自发性脑内出血是年龄相关性认知功能下降的重要因素。 医生经常遗漏诊断，因为出现的症状类似于中风，并可能进一步 超过80%的阿尔茨海默病患者存在复杂的动脉粥样硬化。疑似CAA的标准诊断 包括昂贵的成像技术和侵入性脑活检。诊断慢性再生障碍性贫血的唯一权威方法 是通过尸检分析。需要能够在早期可靠地识别CAA的生前诊断， 无症状阶段，使正确的诊断能够避免疾病中禁忌的药物，这是 会增加个人的中风风险。此外，需要一个有用和负担得起的结果标志来 临床试验的重点是可以阻止或逆转疾病进展的CAA治疗方法。阿米迪斯 旨在通过识别眼睛中的来解决这些未得到满足的需求，将其作为大脑的窗口，用于早期检测 CAA。Amydis正在开发一种新的视网膜诊断探头来满足这一需求。我们的新型视网膜 诊断探头AMDX-2011P具有可用于标准视网膜成像的荧光特性 在眼科医生办公室发现的设备和波长适合与常规 仪器，当系统地以显著的浓度给药时，它穿透视网膜，是无毒的 临床前动物模型，并具有结晶特性，允许一致的大规模生产。在……里面 根据这项提案，AMDIS将按照GMP指南生产AMDX-2011P，并将AMDX-2011P用于静脉注射。 给药，测试稳定性，然后在健康受试者中进行单次递增剂量的1期临床试验 (n=24)，然后在一小部分CAA患者(N=5)中测试最佳剂量。完成这些目标将 推动我们体内眼科诊断测试的发展，使我们离我们的使命又近了一步 提供一种临终前、简单和负担得起的CAA诊断。