Ex Vivo Tolerance for Xenotransplantation of Diabetes P2

糖尿病 P2 异种移植的体外耐受性

• 批准号: 8314227
• 负责人: Luca Inverardi
• 金额: $ 100万
• 依托单位: XIMEREX, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8314227
• 关键词: Achievement; Address; Antibodies; Antigens; Applications Grants; Beta Cell; Biotechnology; Bone Marrow; Businesses; Capital; Cell Transplants; Cells; Cessation of life; Chronic; Clinical; Clinical Protocols; Clinical Trials; Critiques; Development; Development Plans; Diabetes Mellitus; Disease; Failure; Family suidae; Funding; Glucose; Glycosylated hemoglobin A; Goals; Growth Factor; Guidelines; Heart Transplantation; Hematopoietic; Housing; Human; Immune Tolerance; Immunosuppression; Implant; Insulin; Insulin-Dependent Diabetes Mellitus; Investments; Islet Cell; Islets of Langerhans; Islets of Langerhans Transplantation; Knowledge; Lead; Legal; Legal patent; Lymphocyte; Macaca mulatta; Maintenance; Malignant neoplasm of brain; Measures; Medical; Mentors; Monitor; Monkeys; Natural Killer Cells; Normal Range; Outcome; Patients; Performance; Pharmaceutical Preparations; Phase; Portal vein structure; Positioning Attribute; Process; Production; Qualifying; R43 grant; Reaction; Recommendation; Regulatory T-Lymphocyte; Research Institute; Resistance; Sheep; Small Business Innovation Research Grant; Source; Spleen; Streptozocin; Suggestion; Suppressor-Effector T-Lymphocytes; Technology; Tissues; Transplant Recipients; Transplantation; Transplanted tissue; United States National Institutes of Health; Universities; Widespread Disease; Work; Xenograft procedure; base; clinical application; commercialization; diabetic; diabetic patient; experience; fetal; innovation; intravenous drip; islet; nonhuman primate; pre-clinical; preclinical study; prevent; programs; prospective; success; symposium; tissue processing

DESCRIPTION (provided by applicant): Type I diabetes is a widespread disease in which insulin producing pancreatic islets are lost, leading to unstable glucose levels. If the islets can be replaced, as with transplantation, then diabetes can be reversed. Human islets have limited utility because of a severe shortage of donors and the need for constant immune suppression to prevent rejection. Pigs could provide an unlimited supply of islets but the rejection would be even more vigorous, necessitating greater immune suppression. Ximerex, Inc. has developed an innovative and proprietary technology known as surrogate tolerogenesis (ST). With ST pig islets can be transplanted without rejection or immune suppression. ST is supported by extensive proof of principle, including pig islets to diabetic monkey transplants with prolonged survival and function without immune suppression. The program was recently reviewed by the NIH commercialization assistance program (CAP). A large panel of experts in business development concluded that the technology does provide a strong competitive advantage and is protected by a robust patent portfolio. However, the regulatory hurdles are substantial, requiring FDA approval for commercialization. Ximerex, Inc. is unlikely to attract private investments until the FDA allows phase I/II trails. Many specific suggestions were made. RFA-OD-09008 (an RC3 BRDG-SPAN pilot program) targets small companies such as Ximerex, Inc. in the "Valley of Death", i.e. with extensive proof of principle but unable to attrac investors. This proposal takes the steps necessary for initial clinical trials and subsequent investment based development. Specifically, it includes a large definitive pig to nonhuman primate transplant study to establish efficacy of ST to the FDA; recruitment of a chief medical officer for planning clinical trials and interacting with the FDA; and development of facilities and labs for the FDA certified swine source herd and tissue processing. Furthermore, this proposal transforms the program from one based on the founder to a multi-institutional partnership, including the University of Miami-Diabetes Research Institute with their wealth of knowledge and facilities. PUBLIC HEALTH RELEVANCE: While developing our technologies in the field of transplantation, we have measured our progress with both success and failure. Through these trials we have developed a simple idea into what may change our ability to treat disease, putting transplantation of porcine tissues into the limelight. This project fully develops transplantation f pig islets into diabetic patients without rejection of the tissue and without the need for immune suppression. The aims of this project will demonstrate the recent refinements to the technology and lead to initial clinical trials.

描述（由申请人提供）：I型糖尿病是一种广泛的疾病，其中胰岛素产生胰岛丢失，导致葡萄糖水平不稳定。如果胰岛可以 被替换为移植，然后可以逆转糖尿病。人类胰岛的效用有限，因为捐助者严重短缺以及需要持续的免疫抑制以防止排斥。猪可以提供无限的胰岛供应，但排斥更加有力，需要更大的免疫抑制。 Ximerex，Inc。开发了一种创新的专有技术，称为替代耐受生成（ST）。使用St Pig胰岛可以移植而无需排斥或免疫抑制。 ST得到了广泛的原理证明，包括对糖尿病猴移植的猪胰岛，生存期延长而功能，而没有免疫抑制。 NIH商业化援助计划（CAP）最近对该计划进行了审查。大量业务发展专家小组得出结论，该技术确实提供了强大的竞争优势，并受到强大的专利组合的保护。但是，监管障碍是重大的，需要FDA批准进行商业化。 Ximerex，Inc。不太可能吸引私人投资，直到FDA允许I/II阶段步道。提出了许多具体的建议。 RFA-OD-09008（一个RC3 BRDG-SPAN试点计划）针对的是Ximerex，Inc。等小公司的“死亡山谷”，即具有广泛的原则证明，但无法获得投资者。 该提案采取了初步临床试验和随后基于投资的开发所需的步骤。具体而言，它包括一只大量的确定性猪到非人类灵长类动物移植研究，以确立ST对FDA的功效。招募首席医疗官 计划临床试验并与FDA互动；以及开发FDA认证的猪来源群和组织加工的设施和实验室。此外，该提案将该计划从基于创始人的计划转变为多机构的合作伙伴关系，包括迈阿密 - 糖果大学研究所，及其丰富的知识和设施。 公共卫生相关性：在移植领域开发我们的技术时，我们已经通过成功和失败来衡量我们的进步。通过这些试验，我们将一个简单的想法发展为改变我们治疗疾病的能力，将猪组织移植到众人瞩目的焦点中。该项目充分发展了猪胰岛，而无需拒绝组织，而无需免疫抑制。该项目的目的将证明该技术的最新改进并导致初步的临床试验。