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

该小型企业创新研究计划（SBIR）I期项目的更广泛影响/商业潜力将是一种安全的血管内解毒器械，用于治疗多种急性和慢性病变。该装置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，还将为普通人群安全使用病毒基因治疗开辟道路。它有可能降低死亡率，并减轻广泛的抗体介导的病理状况对全球医疗保健支出的负担。社会需要一种安全、成本有效、快速作用、广泛可及且易于使用的系统，其能够快速血液解毒以治疗病理状况。该设备的目标市场包括价值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，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。I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，以治疗IgG驱动的病理状况。 抗体介导的免疫应答是导致自身免疫性疾病、移植排斥反应、病毒基因治疗中免疫介导的排斥反应等多种急、慢性疾病的关键因素。目前，治疗性单采和强效全身免疫抑制剂已成为IgG驱动的病理的主要管理形式。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。所提出的血管内血液IgG解毒装置可以潜在地提供循环IgG的安全和快速消除，消除对不利或有害治疗的需要，例如治疗性单采或强效全身免疫抑制剂。将在离体静脉模拟系统中对该器械进行全面研究，测试其血液相容性、IgG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一个致命的IgG诱导的免疫性血小板减少性紫癜（ITP）模型在小型猪中进行研究。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.