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

这个小企业创新研究计划(SBIR)第一阶段项目的更广泛的影响/商业潜力将是一种安全的血管内戒毒设备，用于治疗多种急慢性疾病。建议的设备可以帮助治疗严重的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治疗扫清一条道路。对于普遍存在的抗体介导的病理疾病，它具有降低死亡率和减轻全球医疗支出负担的潜力。社会上需要一种安全、经济、快速、易获得、易于使用的系统，能够快速排出血液毒素用于治疗病理疾病。拟议中的设备瞄准的市场包括数十亿美元的自身免疫性疾病、器官移植排斥反应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。这个小企业创新研究计划(SBIR)第一阶段项目支持开发一个血管内血液IgG解毒平台，用于快速消除用于治疗IgG驱动的病理疾病的IgG抗体。在病毒基因治疗中，抗体介导的免疫反应是导致包括自身免疫性疾病、移植排斥反应、免疫介导排斥反应在内的多种急、慢性疾病的关键因素。目前，治疗性分离和有效的全身性免疫抑制剂已成为治疗免疫球蛋白引起的病理的主要形式。然而，这些形式的治疗对患者并不友好，在许多情况下弊大于利。建议的血管内血液免疫球蛋白解毒装置可能提供安全和快速清除循环中的免疫球蛋白，消除不利或在情况下有害的治疗的需要，如治疗性分离或有效的全身免疫抑制剂。该装置将在体外静脉模拟系统中进行全面的研究，测试其血液相容性、免疫球蛋白清除能力，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，该设备的安全性、耐用性、免疫反应和治疗效果将在小型猪的致死性免疫球蛋白诱导的免疫性血小板减少性紫癜(ITP)模型中进行调查。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.