Development of a novel ophthalmic probe for cerebral amyloid angiopathy

开发用于脑淀粉样血管病的新型眼科探针

• 批准号: 9907957
• 负责人: Stella Sarraf
• 金额: $ 49.03万
• 依托单位: AMYDIS DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907957
• 关键词: Address; Advanced Development; Age; Age-associated memory impairment; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Amyloidosis; Animal Model; Arteries; Autopsy; Binding; Biological Markers; Biopsy; Blood Vessels; Brain; Brain hemorrhage; Canis familiaris; Caring; Cerebral Amyloid Angiopathy; Cerebral hemisphere hemorrhage; Cerebrum; Chemistry; Clinic; Clinical; Clinical Research; Clinical Trials; Deposition; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Dose; Drug Kinetics; Early Diagnosis; Elderly; Eye; Fluorescence; Fluorescent Probes; Formulation; Goals; Hand; Histopathology; Human; Imaging Techniques; In Vitro; Investigational Drugs; Lead; Legal patent; Libraries; Magnetic Resonance Imaging; Metabolism; Mission; Monitor; Neuraxis; Neurologist; One-Step dentin bonding system; Outcome; Patient Care; Patients; Peptides; Pharmaceutical Preparations; Pharmacology; Phase; Physicians; Preparation; Procedures; Process; Prodrugs; Property; Rattus; Reporting; Research; Retina; Retinal; Risk; Safety; Specialist; Stroke; Symptoms; Technology; Testing; Tissues; Toxic effect; Transgenic Mice; Validation; Work; base; brain tissue; chemical synthesis; clinical candidate; design; diagnosis standard; experimental study; genotoxicity; healthy volunteer; improved; in vivo; innovation; inorganic phosphate; meetings; metabolic abnormality assessment; mouse model; novel; off-patent; preclinical study; small molecule; standard care; standard of care; stroke risk; 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 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 ante-mortem diagnostic is needed that can reliably identify CAA at the early, asymptomatic stages, enabling a correct diagnosis to avoid medications contraindicated in the disease. Furthermore, a useful and affordable outcome marker is needed for clinical trials focused on therapies for CAA that could stop or reverse 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. Several amyloid forming peptides can lead to CAA, among them, amyloid beta (1-40), Aβ40, is by far the most prevalent form. Amydis’ probes have demonstrated significant fluorescence enhancement in vitro with synthetically aggregated Aβ40, the ability to detect retinal amyloid deposits in vivo in transgenic mouse models, and detection of amyloid deposits ex vivo with human brain tissue from CAA patients. We have selected our lead clinical candidate, AMDX- 2011P, based on properties amenable for commercial development. With this proposal we aim to 1) develop a chemical synthesis and formulation of AMDX-2011P in preparation for clinical trials, 2) complete preclinical studies to assess the metabolism, pharmacokinetics and toxicity of AMDX- 2011P and 3) complete investigational new drug (IND) enabling studies to file an IND with the FDA. Completion of these aims will advance the development of our in vivo ocular diagnostic test into human clinical trials, getting us one step closer to our mission of providing an ante-mortem, simple and affordable CAA diagnostic.

项目总结