Imaging Brain Amyloid with a Bispecific Antibody

使用双特异性抗体对脑淀粉样蛋白进行成像

• 批准号: 6929525
• 负责人: YUN ZHANG
• 金额: $ 10万
• 依托单位: ARMAGEN TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-25 至 2005-10-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6929525
• 关键词: Alzheimer' s disease; CHO cells; affinity chromatography; amyloid proteins; biotechnology; blood brain barrier; brain imaging /visualization /scanning; diagnosis design /evaluation; disease /disorder prevention /control; early diagnosis; electroporation; enzyme linked immunosorbent assay; genetic manipulation; genetic techniques; hybrid antibody; immunologic substance development /preparation; ion exchange chromatography; mass spectrometry; molecular cloning; monoclonal antibody; polymerase chain reaction; protein quantitation /detection; radiopharmacology; reagent /indicator; single photon emission computed tomography; western blottings

DESCRIPTION (provided by applicant): The dementia of Alzheimer's Disease (AD) is caused by the slow accumulation of brain 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 Alzheimer'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 bispecific antibody, wherein one monoclonal antibody (MAb) is a chimeric MAb to the human insulin receptor (HIR), and designated HIRMAb, and the other MAb is a single chain ScFv antibody directed at the Abeta amyloid that forms the plaque of AD, and is designated AbetaMAb. The HIRMAb will enable transport across the BBB and the AbetaMAb will bind the Abeta plaque of AD and enable imaging of the brain amyloid. The drug will contain a chelator moiety for radiolabeling with 111-indium, which will enable imaging of brain amyloid with single photon emission computed tomography, which is widely available in most hospitals and imaging centers. In phase I, the fusion gene will be engineered, cell lines will be transfected, and the bi-functionality of the fusion protein will be demonstrated, as it will be shown that the fusion protein both binds the BBB receptor and binds the AD amyloid. This 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 early detection of those individuals at risk for later development of brain amyloid and AD, and permit early drug therapy.

描述（由申请人提供）：阿尔茨海默氏病的痴呆症（AD）是由脑淀粉样蛋白的缓慢积累引起的。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。这项工作的目的是发展阿尔茨海默氏病（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。 This work will prepare a genetically engineered bispecific antibody, wherein one monoclonal antibody (MAb) is a chimeric MAb to the human insulin receptor (HIR), and designated HIRMAb, and the other MAb is a single chain ScFv antibody directed at the Abeta amyloid that forms the plaque of AD, and is designated AbetaMAb. Hirmab将使跨BBB的运输能够运输，而Abetamab将结合AD的Abeta斑块并实现脑淀粉样蛋白的成像。该药物将包含一个螯合剂部分，用于带有111个印度的放射性标记，该部分将通过单个光子发射计算机断层扫描进行成像，在大多数医院和成像中心都可以广泛使用。在第一阶段，将对融合基因进行设计，将转染细胞系，并将证明融合蛋白的双功能，因为它将表明融合蛋白都结合了BBB受体并结合AD淀粉样蛋白。这项工作将使IND为FDA进行准备，以测试这种小说在体内脑扫描中，这将是第一个针对AD的诊断测试。 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。