OTHER FUNCTIONS-SBIR TOPIC 66 PHASE I: HAPTOGLOBIN TREATMENT TO REDUCE COMPLICAT

其他功能-SBIR 主题 66 第一阶段：触珠蛋白治疗以减少并发症

• 批准号: 8564217
• 负责人: HIROSHI MIZUKAMI
• 金额: $ 14.82万
• 依托单位: NANOSHELL COMPANY, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8564217
• 关键词: Antibodies; Binding; Blood; Blood Component Removal; Centrifugation; Complex; Haptoglobins; Harvest; Hemoglobin; Human; In Vitro; Injection of therapeutic agent; Liver; Metabolic; Oxidative Stress; Patients; Phase; Plasma; Process; Production; Recycling; Saline; Sickle Cell; Sickle Cell Anemia; Small Business Innovation Research Grant; Uncertainty; crosslink; density; macrophage; nanoparticle; scale up

To reduce oxidative stress of patients with sickle cell anemia, the solicitation calls for harvesting hemoglobin-binding haptoglobin from the donated blood and intravenously injecting haptoglobin to the patient to capture and process free sickle cell hemoglobin in the blood. Polymorphic haptoglobins are to be extracted from the Cohen's fraction V or equivalent. Haptoglobin forms a complex with hemoglobin and the complex is recognized with CD-163 macrophages followed by metabolic decomposition in the liver and the components recycled. What is not certain, however, is if the patient is capable of synthesizing additional CD-163 scavenger bound macrophages to process and metabolize the additional sickle cell hemoglobin bound haptoglobin formed by haptoglobin injection. To circumvent this uncertainty, anti-haptoglobin antibodies will be attached to proprietary centrifugally retrievable high-density nano-particles to form rNA, and let it bind with haptoglobin (Hp) in the healthy human plasma to form rNHp. Second, the synthesized rNHp wil be injected to the patients to bind sickle cell hemoglobin (HbS) to form the super-complex (rNHp-HbS), which will be retrieved with aphaeresis.

为了减少镰状细胞性贫血患者的氧化应激，该征集要求从捐献的血液中收集与血红蛋白结合的接触珠蛋白，并向患者静脉注射接触珠蛋白，以捕获和处理血液中的游离镰状细胞血红蛋白。从科恩分数V或同等分数中提取多态触珠蛋白。触珠蛋白与血红蛋白形成复合物，该复合物被CD-163巨噬细胞识别，随后在肝脏中代谢分解并回收其成分。然而，尚不确定的是，患者是否能够合成额外的CD-163清道夫结合巨噬细胞来处理和代谢额外的镰状细胞血红蛋白结合的接触珠蛋白，这些接触珠蛋白是由接触珠蛋白注射形成的。为了避免这种不确定性，将抗触珠蛋白抗体附着在专有的离心可回收的高密度纳米颗粒上形成rNA，并使其与健康人血浆中的触珠蛋白（Hp）结合形成rNHp。第二步，将合成的rNHp注射到患者体内，与镰状细胞血红蛋白（HbS）结合形成超复合物（rNHp-HbS），用分离术回收。