[18F]NAV4694 Imaging to Identify MCI Patients at Risk for Alzheimer's Dementia

[18F]NAV4694 成像识别有阿尔茨海默氏痴呆风险的 MCI 患者

• 批准号: 8867686
• 负责人: Frederick Oliver Cope
• 金额: $ 125.74万
• 依托单位: NAVIDEA BIOPHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8867686
• 关键词: Acute; Address; Aging; Alzheimer' s Disease; American; Amyloid beta-Protein; Biological Products; Brain; Cessation of life; Characteristics; Clinical Data; Clinical Research; Clinical Trials Design; Contracts; Dementia; Deposition; Development; Diagnostic; Diagnostic Imaging; Disease; Elderly; Epidemic; FDA approved; Future; Grant; Health; Health Care Costs; Histopathology; Image; Impaired cognition; Individual; Institutional Review Boards; Investigation; Label; Life; Monitor; Neurobehavioral Manifestations; Neurodegenerative Disorders; Noise; Outcome; Participant; Pathology; Patient Recruitments; Patients; Performance; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Physicians; Population; Positron-Emission Tomography; Quality of Care; Recruitment Activity; Relative (related person); Risk; Safety; Scanning; Signal Transduction; Site; Small Business Innovation Research Grant; Specificity; Statistical Data Interpretation; Symptoms; Time; Training; Validation; base; commercialization; drug candidate; end of life; experience; healthy volunteer; high risk; improved; mild cognitive impairment; performance site; preclinical study; prevent; prospective

DESCRIPTION (provided by applicant): Navidea Biopharmaceuticals is developing [18F]NAV4694 as a diagnostic imaging agent that can be used to visualize beta-amyloid (A) plaques in the brains of living individuals. Alzheimer's disease is the leading cause of dementia. All patients with dementia caused by Alzheimer's disease have abundant A plaques in their brains. There is a great need to develop better means to identify individuals who are at high risk of developing dementia caused by Alzheimer's disease before their symptoms become severe. This need has arisen from the extensive efforts of many companies to develop new and better therapies for this dreaded disease. Ninety such candidate Alzheimer's therapies are currently under investigation. Due to the mechanisms of action of a large portion of these drug candidates, they are likely to be most effective when given to patients before they have significant dementia. The intent of these new therapies will be to prevent or delay the progression of their illnesses to frank dementia. The problem addressed by this proposal is how to best indentify these patients. A plaques begin to appear in the brains of Alzheimer's patients many years before they develop dementia. We recognize, as others, many individuals with A plaques never develop dementia. However, A plaques are indicative of Alzheimer's pathology, and once a patient with A plaques begins to experience cognitive decline, they are at high risk of progression to Alzheimer's dementia. When people with Alzheimer's pathology (i.e. A plaques) first experience cognitive symptoms, their symptoms are minimal. Such people are said to have Mild Cognitive Impairment (MCI). However, MCI can have many causes besides Alzheimer's pathology. Patients with MCI and the underlying pathology associated with Alzheimer's would be candidates for treatment with the new Alzheimer's disease modifying therapies currently under development, while MCI patients with other pathologies would not. In the proposed study, patients with MCI will be imaged with [18F]NAV4694 using positron emission tomography (PET) to identify those individuals with A plaques in their brains. All participants in the study will then be followed for at least 18 months to determine which individuals progress to frank Alzheimer's dementia. It is expected that all participants that progress to frank Alzheimer's dementia will have had evidence of A plaques that were visualized by [18F]NAV4694, while none of the participants lacking A plaques will have progressed to defined Alzheimer's dementia. Thereby, evidence will have been obtained indicating that [18F]NAV4694 imaging could be used to identify the portion of all MCI patients that is at high risk for developing Alzheimer's dementia. Other firms are also developing A imaging agents; however, Navidea Biopharmaceuticals believes, based on its recent clinical data directly contrasting [18F]NAV4694 vs. [18F]PIB, that the superior performance characteristics of [18F]NAV4694 compared to its competitors will make it the preferred imaging agent for this application.

描述(由申请人提供)：Navidea BiopPharmticals正在开发[18F]NAV4694作为一种诊断成像剂，可用于显示活人大脑中的β-淀粉样蛋白(A)斑块。阿尔茨海默病是导致痴呆症的主要原因。所有阿尔茨海默病引起的痴呆症患者的大脑中都有丰富的A斑块。非常需要开发更好的手段，在症状变得严重之前识别出阿尔茨海默病引起痴呆症的高危人群。这种需求源于许多公司为这种可怕的疾病开发新的更好的治疗方法的广泛努力。90种这样的阿尔茨海默氏症候选疗法目前正在调查中。由于这些候选药物中很大一部分的作用机制，在患者出现严重痴呆症之前给他们服用可能是最有效的。这些新疗法的目的将是防止或延缓他们的疾病发展为坦率的痴呆症。这项提案解决的问题是如何最好地识别这些患者。阿尔茨海默氏症患者在发展为痴呆症的许多年前就开始在大脑中出现斑块。我们认识到，像其他人一样，许多患有A斑块的人永远不会患上痴呆症。然而，A斑块是阿尔茨海默氏症病理的标志，一旦A斑块患者开始经历认知能力下降，他们就有很高的风险进展为阿尔茨海默氏症。当患有阿尔茨海默氏病(即斑块)的人第一次出现认知症状时，他们的症状是轻微的。这类人被称为轻度认知障碍(MCI)。然而，除了阿尔茨海默氏症的病理之外，MCI还可能有许多原因。患有MCI和与阿尔茨海默氏症相关的潜在病理的患者将是目前正在开发的新的阿尔茨海默病修改疗法的候选患者，而患有其他病理的MCI患者则不会。在这项拟议的研究中，MCI患者将使用正电子发射断层扫描(PET)对[18F]NAV4694进行成像，以识别那些大脑中有A斑块的人。然后，研究中的所有参与者将被跟踪至少18个月，以确定哪些人进展为坦率的阿尔茨海默氏症。预计所有进展为坦率阿尔茨海默氏症的参与者都将有[18F]NAV4694可视化的A斑块的证据，而没有A斑块的参与者都不会进展为明确的阿尔茨海默氏症。因此，已经获得的证据表明，[18F]NAV4694成像可以用来识别所有MCI患者中发展为阿尔茨海默氏病的高风险部分。其他公司也在开发A类显像剂；然而，Navidea BiopPharmticals认为，根据其最近直接对比[18F]NAV4694和[18F]PIB的临床数据，与其竞争对手相比，[18F]NAV4694的卓越性能特征将使其成为这一应用的首选成像剂。