SBIR Phase I: Endovascular Device for Treatment of IgG-Driven Pathological Conditions

这项小企业创新研究计划（SBIR）一期项目的广泛影响和商业潜力将是一种安全的血管内解毒装置，用于治疗许多急慢性疾病。该装置可以帮助治疗严重自身免疫性疾病患者和器官移植患者，此外，将为在普通人群中安全使用病毒基因疗法开辟道路。它有可能降低死亡率，减轻广泛存在的抗体介导的病理状况对全球卫生保健支出的负担。社会需要一种安全、具有成本效益、快速、广泛可及和易于使用的系统，能够快速血液解毒，用于治疗病理状况。该设备的目标市场包括数十亿美元的自身免疫性疾病、器官移植排斥和病毒基因治疗市场，其中最大的市场机会是全球自身免疫性疾病治疗市场，预计到2025年将达到1533亿美元。这项小型企业创新研究计划（SBIR）一期项目支持开发血管内血液IgG解毒平台，用于快速消除IgG抗体，用于治疗IgG驱动的病理状况。在病毒基因治疗中，抗体介导的免疫反应是许多急慢性病理疾病的关键因素，包括自身免疫性疾病、移植排斥反应、免疫介导的排斥反应。目前，治疗性分离和有效的全身免疫抑制剂已成为治疗igg驱动病变的主要形式。然而，这些形式的治疗对病人并不友好，在许多情况下弊大于利。提出的血管内血液IgG解毒装置可能提供安全和快速消除循环中的IgG，消除了不利的或在某些情况下有害的治疗，如治疗性采血或强效全身免疫抑制剂的需要。该装置将在离体静脉模拟系统中进行全面研究，测试其血液相容性、igg消除能力，以及不同参数（包括棒材料、棒直径、棒长度、流速和治疗蛋白浓度）的影响。此外，该装置的安全性、耐久性、免疫反应和治疗效果将在致死性igg诱导的小型猪免疫性血小板减少性紫癜（ITP）模型中进行研究。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research Program (SBIR) Phase I project will be a safe endovascular detoxification device for treatment of numerous acute and chronic pathologies. The proposed device could aid in the treatment of severe autoimmune disease patients and organ transplant patients, and furthermore, would clear up a path for safe use of viral gene therapy in the general population. It has the potential to decrease mortality and reduce the burden on the global healthcare expenditure for the widespread antibody-mediated pathological conditions. There is a societal need for a safe, cost-effective, fast-acting, widely-accessible, and easy-to-use system capable of rapid blood detoxification for treatment of pathological conditions. The markets targeted by the proposed device include the multibillion-dollar autoimmune disease, organ transplant rejection, and viral gene therapy markets, with the largest market opportunity being the global autoimmune disease therapeutics market that is expected to reach $153.3 billion by 2025.This Small Business Innovation Research Program (SBIR) Phase I project supports the development an endovascular blood IgG detoxification platform for rapid elimination of IgG antibodies for treatment of IgG-driven pathological conditions. Antibody-mediated immune response has been a key factor responsible for numerous acute and chronic pathological conditions including autoimmune diseases, transplant rejections, immune-mediated rejection in viral gene therapy. Currently, therapeutic apheresis and potent systemic immunosuppressives have been the main forms of management for IgG-driven pathologies. However, these forms of treatments are not patient-friendly, and in many cases do more harm than good. The proposed endovascular blood IgG detoxification device could potentially provide safe and rapid elimination of circulating IgGs, eliminating the need for unfavorable or in cases harmful treatments such as therapeutic apheresis or potent systemic immunosuppressives. The device will be comprehensively investigated in an ex vivo venous simulation system, testing its hemocompatibility, IgG-elimination capacity, and the influence of different parameters including rod material, rod diameter, rod length, flow rate, and therapeutic protein concentration. Furthermore, the safety, durability, immune response, and therapeutic efficacy of the device will be investigated in a lethal IgG-induced immune thrombocytopenic purpura (ITP) model in minipigs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.