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乳糜泻的当前及新型治疗策略

Current and novel therapeutic strategies in celiac disease.

作者信息

Kurada Satya, Yadav Abhijeet, Leffler Daniel A

机构信息

a Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , MA , USA.

b Department of Medicine, Boston Medical Center , Boston University School of Medicine , Boston , MA , USA.

出版信息

Expert Rev Clin Pharmacol. 2016 Sep;9(9):1211-23. doi: 10.1080/17512433.2016.1200463. Epub 2016 Jun 23.

Abstract

INTRODUCTION

A gluten free diet (GFD) is the only available treatment for celiac disease (CD). However many patients fail to respond fully clinically or histologically. Several surveys highlight the psychosocial implications of adherence to a GFD. Hence, efforts are ongoing to develop therapeutic strategies beyond a GFD.

AREAS COVERED

We conducted a search of PubMed and clinicaltrials.gov to extract articles on CD using keywords including 'celiac disease' and 'refractory celiac disease' (RCD) and focused on articles conducting pathophysiologic and therapeutic research in/ex-vivo models and human trials. We highlight novel therapeutics that manipulate these mechanisms including tight junction regulators, glutenases, gluten sequestrants and immunotherapy using vaccines, nanoparticles that may serve as adjuncts to a GFD or more ambitiously to allow for gluten consumption. We also highlight the role of anti-inflammatories, immunosuppressants and monoclonal antibodies in RCD. Expert commentary: Therapeutics including tight junction regulators, glutenases have the potential to be approved for non-responsive CD or as gluten adjuncts. We expect results of various phase 1/2 trials using AMG 714, BL 7010, IgY antibodies to be published. In the interim, off-label use of 5 amino-salicylates, budesonide, nucleoside analogues and newer biologics developed for other inflammatory diseases will be used in RCD.

摘要

引言

无麸质饮食(GFD)是乳糜泻(CD)唯一可用的治疗方法。然而,许多患者在临床或组织学上并未完全缓解。多项调查强调了坚持GFD的社会心理影响。因此,人们正在努力开发超越GFD的治疗策略。

涵盖领域

我们在PubMed和clinicaltrials.gov上进行了检索,以提取有关CD的文章,关键词包括“乳糜泻”和“难治性乳糜泻”(RCD),并重点关注在体内/体外模型和人体试验中进行病理生理学和治疗研究的文章。我们重点介绍了操纵这些机制的新型疗法,包括紧密连接调节剂、谷氨酰胺酶、麸质螯合剂以及使用疫苗的免疫疗法、纳米颗粒,这些可能作为GFD的辅助手段,或者更理想的是允许食用麸质。我们还强调了抗炎药、免疫抑制剂和单克隆抗体在RCD中的作用。专家评论:包括紧密连接调节剂、谷氨酰胺酶在内的疗法有可能被批准用于治疗无反应性CD或作为麸质辅助剂。我们期待使用AMG 714、BL 7010、IgY抗体进行的各种1/2期试验结果能够发表。在此期间,5-氨基水杨酸、布地奈德、核苷类似物以及为其他炎症性疾病开发的新型生物制剂的标签外使用将用于RCD的治疗。

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