Modulating the Natural History of Type 1 Diabetes in Children at High Genetic Risk by Mucosal Insulin Immunization
Modulating the Natural History of Type 1 Diabetes in Children at High Genetic Risk by Mucosal Insulin Immunization
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DOI：
10.1007/s11892-008-0017-y
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发表时间：
2008-04-01
影响因子：
4.2
通讯作者：
Bonifacio, Ezio
中科院分区：
文献类型：
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作者：
Achenbach, Peter;Barker, Jennifer;Bonifacio, Ezio
胰岛素的粘多糖给药代表了预防1型糖尿病的有吸引力的抗原特异性治疗方法。它可以在动物模型中预防自身免疫性糖尿病，但尽管它已被证明是安全的，但尚未在人类研究中被证明有效。疗效可能取决于胰岛素给药的剂量和途径、开始治疗的1型糖尿病发病阶段以及接受治疗的研究队列。我们已经提出了Pre-POINT（初级口服/鼻内胰岛素试验），这是一项针对胰岛自身抗体阴性儿童的初级粘膜胰岛素治疗的剂量探索安全性和免疫有效性初步研究，这些儿童具有1型糖尿病的高遗传风险，自然首先对胰岛素产生自身免疫。Pre-POINT旨在确定耐受性良好的最佳胰岛素剂量和应用途径（口服或鼻内），并可诱导对胰岛素的免疫应答，用于高危儿童的II/III期一级预防试验。
Mucosal administration of insulin represents an attractive antigen-specific therapeutic approach to preventing type 1 diabetes. It can prevent autoimmune diabetes in animal models, but although it has been shown to be safe, it has not yet been proven effective in human studies. Efficacy may depend on the dose and route at which insulin is administered, the stage in type 1 diabetes pathogenesis at which treatment is initiated, and the study cohort that is treated. We have proposed Pre-POINT (Primary Oral/intranasal INsulin Trial), a dose-finding safety and immune efficacy pilot study for primary mucosal insulin therapy in islet autoantibody-negative children at high genetic risk for type 1 diabetes who naturally first develop autoimmunity to insulin. Pre-POINT aims to identify an optimal insulin dose and route of application (orally or intranasally) that is well tolerated and can induce an immune response to insulin for additional use in a phase II/III primary prevention trial in children at risk.