Non-invasive efficient brain delivery of Prussian Blue for treatment of Alzheimer disease

普鲁士蓝无创有效脑部输送治疗阿尔茨海默病

• 批准号: 10092710
• 负责人: Irving Weinberg
• 金额: $ 38.58万
• 依托单位: WEINBERG MEDICAL PHYSICS, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092710
• 关键词: Acute; Adverse effects; Alzheimer' s Disease; Alzheimer' s disease model; Animal Model; Animals; Antioxidants; Blood - brain barrier anatomy; Brain; Bypass; Cognition; Cognitive; Dimensions; Drug Kinetics; Dyes; Family suidae; Goals; Hippocampus (Brain); Histologic; Hour; Human; Image; Inflammation; Injections; Intranasal Administration; Magnetism; Methods; Nose; Oral; Phase; Positron-Emission Tomography; Preparation; Prussian blue; Publishing; Rattus; Rodent; Rodent Model; Safety; Structure of mucous membrane of nose; Testing; Therapeutic; Tissues; Toxic effect; Transgenic Organisms; Work; cytokine; efficacy testing; experience; experimental study; implantation; improved; magnetic field; mortality; nanorod; particle; placebo group; prevent; radiotracer; satisfaction; tau Proteins

Abstract Direct brain injection of radical-scavenging dyes (e.g. Prussian blue) prevents and cures Alzheimer’s disease in animal models. In human tests of orally administered blue dyes, however, reaching therapeutic concentration levels in the brain has not been achievable. Our published rodent experiments have shown that helical magnetic fields can drill magnetic nanorods from the nose into the brain with very high efficiency. Rodent studies have shown no toxicity after 30-days of particle implantation. In the first phase of this fast- track project, we will validate that our magnetic drilling methods can deliver therapeutic levels of blue dye in the brain non-invasively. In the second phase we will verify that this delivery method improves cognition in a rodent model of Alzheimer disease (AD). Accomplishment of this goal will pave the way to human studies, aided by already- committed investors in the project and by experienced academic partners with whom we have worked for over a decade.

摘要 直接脑内注射自由基清除染料（如普鲁士蓝）可预防和治疗 阿尔茨海默病的动物模型。在口服蓝色染料的人体试验中， 然而，在大脑中达到治疗浓度水平还无法实现。 我们发表的啮齿动物实验表明，螺旋磁场可以钻 磁性纳米棒从鼻子进入大脑的效率非常高。啮齿动物研究 在粒子植入30天后没有显示出毒性。在这个快速的第一阶段- 跟踪项目，我们将验证我们的磁性钻孔方法可以提供治疗 非侵入性地检测大脑中蓝色染料的含量在第二阶段，我们将验证这一点， 递送方法改善了阿尔茨海默病（AD）啮齿动物模型的认知。 这一目标的实现将为人类研究铺平道路，并得到已经- 该项目的坚定投资者和经验丰富的学术合作伙伴， 已经工作了十多年