Protecting Pancreatic Islet Grafts from Rejection

描述（由申请人提供）： 1型糖尿病（DM）是一种自身免疫性疾病，其破坏胰腺的胰岛素产生细胞。1型糖尿病影响了大约一百万美国人，通常在年轻人中发病。它是肾脏疾病、周围神经系统疾病和失明的主要原因之一。它主要通过过早的心血管死亡缩短寿命。它导致患者、其家庭和整个社会的重大医疗保健支出。虽然胰岛素替代疗法可以很好地控制血糖水平，但一些糖尿病并发症却不能。因此，重建正常的胰岛功能已成为糖尿病治疗的重要目标。这包括同种异体胰岛移植。免疫抑制方案已经被开发，允许成功移植胰岛。不幸的是，它们充满了显着的直接和慢性副作用，使其使用对儿童特别有问题。目前，只有患有不稳定形式的DM的患者被认为是移植候选者。Isogenis的使命是开发创新的免疫抑制剂，采用高度特异性，但有效的免疫抑制方法。Isogenis的技术基于自然否决免疫抑制现象。Isogenis使用病毒载体转移CD 8 α链，从而对移植物产生特异性免疫抑制。Isogenis已经达到了其否决向量方法的功能实用性证明的关键发展里程碑。Isogenis证实，简单的胰腺外否决载体转导永久保护胰岛免受完全同种异体受体动物的排斥。Isogenis现在提出使用非人灵长类动物模型来测试否决载体的临床版本的功能性、药理学和毒性，从而完成否决载体在胰岛移植中的临床前试验阶段。与此同时，Isogenis将优化否决载体生产和纯化的方案以及基于否决载体的免疫抑制方案。这些研究将允许Isogenis收集数据，以便向“食品和药物管理局”提交“研究性新药”（IND）。 1型糖尿病（DM）是一种自身免疫性疾病，其破坏胰腺的胰岛素产生细胞。据估计，1型糖尿病影响着100万美国人，是肾脏疾病、周围神经系统疾病和失明的主要原因之一。胰岛移植可以提供永久的治愈。然而，目前用于器官移植的免疫抑制方案充满了显着的直接和慢性副作用，使得它们的使用对于儿童尤其成问题。Isogenis正在开发新型免疫抑制化合物，毒性较小，短期使用;但预防移植组织的排斥反应，即使没有改善疗效，也具有相似的效果。

DESCRIPTION (provided by applicant): Type 1 diabetes mellitus (DM) is an autoimmune disease that destroys insulin-producing cells of the pancreas. Type 1 DM affects an estimated one million Americans and usually finds its onset in the young. It is one of the leading causes of kidney disease, peripheral neurological diseases and also blindness. It shortens the lifespan primarily through premature cardiovascular mortality. It results in significant health care expenditures for patients, their families and society as a whole. Although blood glucose levels can be well controlled by insulin substitution therapy, some of the DM complications cannot. Therefore, reconstitution of normal pancreatic islet function has been an important DM treatment goal. This has included the transplantation of allogeneic pancreatic islets. Immune suppression protocols have been developed that allowed the successful transplantation of islets. Unfortunately, they are fraught with significant immediate and chronic side effects that make their use especially problematic for children. Presently, only patients suffering from unstable forms of DM are considered transplantation candidates. Isogenis' mission has been the development of innovative immune inhibitory agents that employ highly specific, yet effective immune suppression approaches. Isogenis based its technology on the natural veto immune inhibitory phenomenon. Isogenis uses viral vectors that transfer the CD8 a-chain and thus specific immune suppression to transplants. Isogenis already reached the crucial developmental milestone of proof-of-functional utility of its veto vector approach. Isogenis established that simple extracorporal veto vector transductions permanent protected pancreatic islets from rejection by fully allogeneic recipient animals. Isogenis now proposes to use a nonhuman primate model to test the functionality, pharmacology and toxicity of the clinical version of a veto vector and thus to complete the pre-clinical trial stage of veto vectors in pancreatic islet transplantation. In parallel, Isogenis will optimize protocols of veto vector production and purification and veto vector-based immune suppression regimens. These studies will allow Isogenis to collect data for the filing of an 'investigational new drug' (IND) with the 'Food and Drug Administration'. Type 1 diabetes mellitus (DM) is an autoimmune disease that destroys insulin-producing cells of the pancreas. Type 1 DM affects an estimated one million Americans and is one of the leading causes of kidney disease, peripheral neurological diseases and also blindness. Transplantation of pancreatic islets can provide a permanent cure. However, present immune suppression regimens used for organ transplantation are fraught with significant immediate and chronic side effects that make their use especially problematic for children. Isogenis is developing novel immune suppressive compounds that are less toxic,a are used short-term; yet prevent the rejection of transplanted tissue with similar if not improved efficacy.