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

脑淀粉样血管病眼科诊断探针的研制

基本信息

批准号：
10253366
负责人：
Stella Sarraf
金额：
$ 159.09万
依托单位：
AMYDIS DIAGNOSTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10253366
关键词：
Address Advanced Development Age Age-associated memory impairment Alzheimer&apos 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 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

项目摘要

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.

项目概要脑淀粉样血管病（CAA）是老年人中常见的神经病理学发现，以大脑血管壁中的淀粉样蛋白 (Aβ) 沉积为特征，是 CAA 的主要原因。自发性脑出血是导致年龄相关认知能力下降的重要因素。医生经常会错过诊断，因为其症状与中风相似，并且可能会进一步恶化。超过 80% 的阿尔茨海默病患者存在 CAA，因此情况很复杂。可能的 CAA 的标准诊断。涉及昂贵的成像技术和侵入性脑活检是诊断 CAA 的唯一确定方法。需要进行死前诊断，以便在早期可靠地识别 CAA。无症状阶段，能够做出正确的诊断，避免使用该疾病禁忌的药物，这会增加个体中风的风险此外，需要一种有用且负担得起的结果标记。临床试验的重点是能够阻止或逆转疾病进展的 CAA 疗法。旨在通过识别眼睛中的 A 来解决这些未满足的需求，A 作为大脑的窗口，可以及早发现 CAA.Amydis 开发了一种新型视网膜诊断探针来满足这一需求。诊断探针 AMDX-2011P 具有荧光特性，适用于标准视网膜成像眼科医生办公室的设备和荧光波长适合使用传统的当以显着浓度全身给药时，它会穿透视网膜，在以下情况下是无毒的：临床前动物模型，并具有允许一致的大规模生产的结晶特性。根据该提案，Amydis 将在 GMP 指南下生产 AMDX-2011P，配制用于静脉注射的 AMDX-2011P。交付，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)，然后在一小群 CAA 患者中测试剂量 (N=5) 将完成这些目标。我们体内先进眼部诊断测试的开发，使我们离我们的使命又近了一步提供生前、简单且经济实惠的 CAA 诊断。