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

基本信息

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
项目类别：
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

项目摘要

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（申请人提供）：阿尔茨海默病（AD）痴呆是由脑部淀粉样蛋白缓慢积累引起的。因此，开发测量大脑淀粉样蛋白的脑部扫描可以识别那些有后期发展为 AD 风险的个体。早期发现可以早期治疗并延迟症状的出现。据估计，仅将 AD 症状的出现延迟 5 年，美国每年就可以节省 500 亿美元的医疗费用。仅在美国，可能接受 AD 诊断性脑部扫描的人数就超过 3000 万。这项工作的目标是开发阿尔茨海默病 (AD) 诊断性脑部扫描。 AD 是由淀粉样蛋白在大脑中沉积引起的，如果淀粉样蛋白显像剂能够通过血脑屏障 (BBB)，则可以对 AD 进行诊断性脑部扫描。这项工作将制备一种基因工程双特异性抗体，其中一种单克隆抗体（MAb）是针对人胰岛素受体（HIR）的嵌合MAb，命名为HIRMAb，另一种MAb是针对Abeta淀粉样蛋白的单链ScFv抗体，形成 AD 斑块，并命名为 AbetaMAb。 HIRMAb 将实现跨 BBB 的运输，而 AbetaMAb 将结合 AD 的 Abeta 斑块并实现大脑淀粉样蛋白的成像。该药物将含有用于用 111-铟进行放射性标记的螯合剂部分，这将能够通过单光子发射计算机断层扫描对脑淀粉样蛋白进行成像，该技术在大多数医院和成像中心都广泛使用。在第一阶段，将设计融合基因，转染细胞系，并证明融合蛋白的双功能，因为将显示融合蛋白既结合BBB受体又结合AD淀粉样蛋白。这项工作将有助于向 FDA 准备 IND，以测试这种新颖的体内脑扫描，这将是第一个针对 AD 的诊断测试。 AD 脑部扫描可以早期发现那些有脑淀粉样蛋白和 AD 后期发展风险的个体，并允许早期药物治疗。