Mayo Clinic, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN 55905, USA.
Expert Opin Drug Discov. 2013 Apr;8(4):445-57. doi: 10.1517/17460441.2013.761203. Epub 2013 Jan 8.
Currently, the only treatment for celiac disease is a gluten-free diet, and there is an increased desire for alternative therapies. In vitro and in vivo models of celiac disease have been generated in order to better understand the pathogenesis of celiac disease, and this review will discuss these models as well as the testing of alternative therapies using these models.
The research discussed describes the different in vitro and in vivo models of celiac disease that currently exist and how they have contributed to our understanding of how gluten can stimulate both innate and adaptive immune responses in celiac patients. We also provide a summary on the alternative therapies that have been tested with these models and discuss whether subsequent clinical trials were done based on these tests done with these models of celiac disease.
Only a few of the alternative therapies that have been tested with animal models have gone on to clinical trials; however, those that did go on to clinical trial have provided promising results from a safety standpoint. Further trials are required to determine if some of these therapies may serve as an effective adjunct to a gluten-free diet to alleviate the adverse affects associated with accidental gluten exposure. A "magic-bullet" approach may not be the answer to celiac disease, but possibly a future cocktail of these different therapeutics may allow celiac patients to consume an unrestricted diet.
目前,治疗乳糜泻的唯一方法是无麸质饮食,但人们对替代疗法的需求日益增加。为了更好地了解乳糜泻的发病机制,已经生成了乳糜泻的体外和体内模型,本综述将讨论这些模型以及使用这些模型测试替代疗法的情况。
所讨论的研究描述了目前存在的不同乳糜泻的体外和体内模型,以及它们如何帮助我们了解麸质如何刺激乳糜泻患者的固有和适应性免疫反应。我们还总结了已用这些模型测试过的替代疗法,并讨论了是否根据这些模型的测试进行了后续临床试验。
只有少数已用动物模型测试过的替代疗法进行了临床试验;然而,那些进行临床试验的替代疗法从安全性角度来看提供了有希望的结果。需要进一步的试验来确定这些疗法中的一些是否可以作为无麸质饮食的有效辅助手段,以减轻偶然摄入麸质带来的不良反应。“灵丹妙药”的方法可能不是乳糜泻的答案,但未来可能是这些不同疗法的组合,使乳糜泻患者可以不受限制地饮食。