Drug Development of an Alzheimer's disease brain scan

阿尔茨海默病脑部扫描的药物开发

• 批准号: 6905592
• 负责人: RUBEN J. BOADO
• 金额: $ 45.75万
• 依托单位: ARMAGEN TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6905592
• 关键词: Alzheimer' s disease; SDS polyacrylamide gel electrophoresis; amyloid proteins; bioimaging /biomedical imaging; biotechnology; blood brain barrier; brain imaging /visualization /scanning; cell line; chimeric proteins; diagnosis design /evaluation; drug design /synthesis /production; immunocytochemistry; mass spectrometry; matrix assisted laser desorption ionization; nervous system disorder diagnosis; protein engineering; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): The dementia of Alzheimer's Disease (AD) is caused by the buildup in the brain over many years of amyloid. Therefore, the development of a brain scan that measures brain amyloid could identify those individuals at risk for the later development of AD. Early detection can lead to early therapy and delay the onset of symptoms. It is estimated that the delay of the onset of symptoms of AD, for just 5 years, would save $50 billion per year in U.S. health care costs. The number of people who are potential candidates for an AD diagnostic brain scan is in excess of 30 million in United States alone. The goal of this work is the development of an AIzheimer's Disease (AD) diagnostic brain scan. AD is caused by the deposition of amyloid in the brain and a diagnostic brain scan for AD could be developed if amyloid imaging agents were made transportable through the blood brain barrier (BBB). This work will prepare a genetically engineered fusion protein wherein the amyloid-imaging agent is fused to a targeting ligand that undergoes receptor-mediated transport across the BBB in vivo. This BBB transport vector has been genetically engineered to enable use in humans without immunological reaction. The fusion protein will be a bi-functional molecule that not only crosses the BBB, but also binds to the amyloid plaques of AD brain in vivo, and contains a chelator moiety for radiolabeling. In phase I, the fusion gene was engineered, cell lines were produced, and the bi-funtionality of the fusion protein was demonstrated--the fusion protein both binds the BBB receptor and binds the AD amyloid. The phase II work will produce a cell line secreting the fusion protein, and the production of this protein will be scaled up for manufacturing. Following the validation of the fusion protein, the pharmacology/toxicology and IND preparation will be performed during the 03 year. The completion of the phase II work will enable the preparation of an IND to the FDA for testing of this novel in vivo brain scan that will be the first diagnostic test specific for AD. The AD brain scan may allow for the early detection of those individuals at risk for later development of brain amyloid and AD, and allow for early drug therapy.

描述（由申请人提供）：阿尔茨海默氏病的痴呆症（AD）是由淀粉样蛋白多年来大脑积聚引起的。因此，测量大脑淀粉样蛋白的脑扫描的开发可以识别出那些有后来发展AD的风险的人。早期发现会导致早期治疗并延迟症状的发作。据估计，仅5年的AD症状发作的延迟将节省每年500亿美元的美国医疗保健费用。仅在美国，可能是广告诊断脑扫描的潜在候选人的人数就超过了3000万。这项工作的目的是开发Aizheimer病（AD）诊断性脑扫描。 AD是由淀粉样蛋白在大脑中的沉积引起的，如果使淀粉样蛋白成像剂可通过血液脑屏障（BBB）运输，则可能开发出AD的诊断性脑扫描。这项工作将准备一种基因工程的融合蛋白，其中淀粉样蛋白成像剂与靶向配体融合在一起，该配体在体内经历了受体介导的跨体内的受体介导的转运。该BBB运输载体已经过基因设计，可以在没有免疫反应的情况下在人类中使用。融合蛋白将是一个双功能分子，不仅可以穿过BBB，而且还与体内AD脑的淀粉样蛋白斑块结合，并包含用于放射性标记的螯合剂部分。在第一阶段，融合基因进行了设计，产生了细胞系，并证明了融合蛋白的双抗衡性 - 融合蛋白都结合了BBB受体并结合AD淀粉样蛋白。 II期的工作将产生分泌融合蛋白的细胞系，该蛋白的生产将缩放以进行制造。融合蛋白验证后，将在03年内进行药理学/毒理学和IND制剂。 II期工作的完成将使IND为FDA进行准备，以测试这款小说在体内脑扫描中，这将是针对AD的首次诊断测试。 AD脑扫描可能会允许早期发现那些有脑淀粉样蛋白和AD发育风险的人，并允许早期药物治疗。