Reduced gluten cereal grains

描述(申请人提供)：乳糜泻(CD)是已知的最常见的食物敏感型肠病，影响大约1%的人口，其发病率似乎正在上升。此外，最近发现，非乳酸面筋敏感性(GS)是一种独特的疾病，影响着越来越多的人。这两种情况都是由面筋引发的，面筋是小麦、大麦和黑麦中发现的一种富含脯氨酸和谷氨酰胺的种子储存蛋白的复杂混合物。由于这些蛋白质对消化具有抵抗力，它们会持续存在于胃肠道中，并在易感人群中引起自体炎症反应。目前，对这些疾病的唯一治疗方法是保持严格的不含葡萄糖的饮食。这项建议将在乳糜泻的非人类灵长类动物模型恒河猴身上，使用大麦和面筋降解酶补充剂来测试低谷蛋白(RG)谷物的安全性。研究表明，当饮食中添加面筋时，恒河猴会患上类似于人类乳糜泻的疾病，而在停止使用面筋后，这种情况会有所改善。在正在进行的研究中，PI一直在鉴定大麦和小麦的低面筋变体，而学术合作者一直在分别开发乳糜泻的动物模型和面筋降解蛋白酶补充剂。对于患有CD或CD的人来说，从饮食中消除所有面筋可能是困难的 使用面筋降解补充剂本身并不是为了允许这些群体恢复不受限制的面筋消费。我们认为，将减谷蛋白谷物与面筋蛋白酶补充剂相结合的协同疗法可能会为这些人提供机会，将有限数量的减谷蛋白谷类引入他们的饮食中。在非人类灵长类动物模型中验证这一假设是拟议研究的目标。这项提议的商业成果将是减少大麦的面筋变体，从而增加对多种食品可接受性的保证。RG大麦代表了一种新的谷类谷物，它可以与其他疗法相结合，为CD和GS患者提供无面筋饮食的替代方案。RG大麦和其他RG谷物的广泛采用可能最终减少这些情况的发生。对RG大麦种子特性的基础知识可能会为RG小麦的研究铺平道路。

DESCRIPTION (provided by applicant): Celiac disease (CD) is the most common food sensitive enteropathy known, affecting approximately 1% of the population and its incidence appears to be on the rise. In addition, non-celiac gluten sensitivity (GS) has recently been revealed to be a distinct condition that affects a growing number of individuals. Both of these conditions are triggered by gluten, a complex mixture of proline and glutamine-rich seed storage proteins found in wheat, barley and rye. Because these proteins are resistant to digestion they persist in the gastrointestinal tract and cause an auto-inflammatory response in susceptible individuals. Currently the only treatment for these conditions is the maintenance of a strict glute free diet. This proposal will test the safety of reduced gluten (RG) cereal grains, using barley a a model cereal, in combination with a gluten degrading enzyme supplement in a non-human primate model of celiac disease, the rhesus macaque. Rhesus macaques have been shown to develop a condition that is analogous to human celiac disease when gluten is included in their diet, and the condition improves upon gluten withdrawal. In ongoing research, the PI has been identifying low gluten variants of barley and wheat, while the academic collaborators have been developing the animal model of celiac disease, and a gluten-degrading protease supplement, respectively. Eliminating all gluten from the diet can be difficult for those suffering from CD or GS, and the use of a gluten degrading supplement by itself is not intended to permit these groups to resume unrestricted gluten consumption. We believe that a synergistic therapy combining reduced gluten grains with a gluten protease supplement may provide the opportunity for these individuals to introduce limited quantities of reduced gluten cereals into their diets. Testing this hypothesis in a non-human primate model is the objective of the proposed research. The commercial outcome of this proposal will be reduced gluten variants of barley for which there will be increased assurance of acceptability for multiple food products. RG barley represents a new category of cereal grain that may play a role in providing an alternative to the gluten free diet for CD and GS individuals in combination with other therapies. The wide adoption of RG barley and other RG grains could ultimately reduce the incidence of these conditions. Basic knowledge about the seed characteristics of RG barley may pave the way for RG wheat.