Reduced gluten cereal grains

描述（由申请人提供）：乳糜泻（CD）是已知最常见的食物敏感性肠病，影响约1%的人口，其发病率似乎呈上升趋势。此外，非乳糜泻麸质敏感性（GS）最近被发现是一种影响越来越多个体的独特疾病。这两种情况都是由麸质引发的，麸质是小麦、大麦和黑麦中富含脯氨酸和谷氨酰胺的种子储存蛋白的复杂混合物。由于这些蛋白质抵抗消化，它们在胃肠道中持续存在，并在易感个体中引起自身炎症反应。目前，治疗这些疾病的唯一方法是维持严格的无麸质饮食。该提案将测试低谷蛋白（RG）谷物的安全性，使用大麦作为模型谷物，结合麸质降解酶补充剂，在非人类乳糜泻灵长类动物模型恒河猴中进行。研究表明，当恒河猴的饮食中含有谷蛋白时，它们会患上一种类似于人类乳糜泻的疾病，而在停止摄入谷蛋白后，这种疾病会得到改善。在正在进行的研究中，PI已经确定了大麦和小麦的低麸质变体，而学术合作者已经分别开发了腹腔疾病的动物模型和麸质降解蛋白酶补充剂。对乳糜泻患者来说，从饮食中剔除所有谷蛋白是很困难的

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.