肽链内切酶
Latiglutenase（以前被称为 ALV003）可以在肠腔内将麸质消化为非抗原性多肽。一项研究未能证明无反应性乳糜泻的总体组织学或症状改善。一项事后多重比较亚组分析发现，尽管采用无麸质饮食，但组织转谷氨酰胺酶 (tTG) 检查呈阳性的乳糜泻患者的症状得到改善。[74]Murray JA, Kelly CP, Green PHR, et al. No difference between latiglutenase and placebo in reducing villous atrophy or improving symptoms in patients with symptomatic celiac disease. Gastroenterology. 2017 Mar;152(4):787-98.https://www.gastrojournal.org/article/S0016-5085(16)35346-X/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/27864127?tool=bestpractice.com[75]Syage JA, Murray JA, Green PHR, et al. Latiglutenase improves symptoms in seropositive celiac disease patients while on a gluten-free diet. Dig Dis Sci. 2017 Sep;62(9):2428-32.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709215/http://www.ncbi.nlm.nih.gov/pubmed/28755266?tool=bestpractice.com
紧密连接调节剂
拉瑞唑来 (Larazotide) 可加强紧密连接并防止麸质渗入黏膜。[76]Leffler DA, Kelly CP, Abdallah HZ, et al. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol. 2012 Oct;107(10):1554-62.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463856/http://www.ncbi.nlm.nih.gov/pubmed/22825365?tool=bestpractice.com研究发现，症状持续的患者的症状得到改善，尽管患者也在坚持无麸质饮食。[76]Leffler DA, Kelly CP, Abdallah HZ, et al. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol. 2012 Oct;107(10):1554-62.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463856/http://www.ncbi.nlm.nih.gov/pubmed/22825365?tool=bestpractice.com
tTG 抑制剂
tTG 抑制剂可防止脱酰胺以及由此导致的醇溶蛋白肽增效作用。[16]Dieterich W, Esslinger B, Schuppan D. Pathomechanisms in celiac disease. Int Arch Allergy Immunol. 2003 Oct;132(2):98-108.http://www.ncbi.nlm.nih.gov/pubmed/14600421?tool=bestpractice.com
醇溶蛋白肽与人类白细胞抗原 (HLA)-DQ2 或 HLA-DQ8 相互作用的阻滞剂
这些药物可防止 T 细胞激活。
免疫调节
免疫调节可恢复对麸质的耐受性。[77]Benahmed M, Mention JJ, Matysiak-Budnik T, et al. Celiac disease: a future without gluten-free diet? Gastroenterology. 2003 Oct;125(4):1264-7.http://www.ncbi.nlm.nih.gov/pubmed/14517809?tool=bestpractice.com 例如，根据 1 期研究，疫苗可以诱导对一些麸质免疫原性肽的免疫耐受。[78]Goel G, King T, Daveson AJ, et al. Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease: two randomised, double-blind, placebo-controlled phase 1 studies. Lancet Gastroenterol Hepatol. 2017 Jul;2(7):479-93.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676538/http://www.ncbi.nlm.nih.gov/pubmed/28506538?tool=bestpractice.com TIMP-GLIA 是一种基于纳米颗粒的药物，正被研究用于治疗乳糜泻。它旨在通过将包被的醇溶蛋白递送至致耐受性免疫细胞来逆转麸质敏感性并促进免疫耐受。1 期临床试验正在招募患者。[79]ClinicalTrials.gov. Study of the safety, tolerability and pharmacokinetics of TIMP-GLIA in subjects with celiac disease. April 2018 [internet publication].https://clinicaltrials.gov/ct2/show/NCT03486990
白细胞介素-15 拮抗剂
经证实，白细胞介素-15 是影响上皮内淋巴细胞存活和黏膜损伤的关键因素。正在研发可阻断这种细胞因子的药物，以用于治疗无反应性和难治性乳糜泻。[80]ClinicalTrials.gov. Study to evaluate the efficacy and safety of AMG 714 in adult patients with type ii refractory celiac disease. February 2018 [internet publication].https://clinicaltrials.gov/ct2/show/NCT02633020
益生菌
早期证据表明，某些益生菌菌株可能对麸质免疫原性起作用，有助于肠道愈合，并改善患者的症状。[81]Smecuol E, Hwang HJ, Sugai E, et al. Exploratory, randomized, double-blind, placebo-controlled study on the effects of Bifidobacterium infantis natren life start strain super strain in active celiac disease. J Clin Gastroenterol. 2013 Feb;47(2):139-47.http://www.ncbi.nlm.nih.gov/pubmed/23314670?tool=bestpractice.com[82]Caminero A, Galipeau HJ, McCarville JL, et al. Duodenal bacteria from patients with celiac disease and healthy subjects distinctly affect gluten breakdown and immunogenicity. Gastroenterology. 2016 Oct;151(4):670-83.http://www.ncbi.nlm.nih.gov/pubmed/27373514?tool=bestpractice.com必须保持谨慎，因为一些益生菌可能是隐匿性麸质的来源。
改良小麦麸质
正在研究各种方法以改变小麦粉中存在的麸质免疫原性肽，从而降低其免疫原性；这些方法包括微波、γ 辐射、乳酸杆菌和真菌蛋白酶水解或基因测序改变。[83]Sánchez-León S, Gil-Humanes J, Ozuna CV, et al. Low-gluten, nontransgenic wheat engineered with CRISPR/Cas9. Plant Biotechnol J. 2018 Apr;16(4):902-10.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867031/http://www.ncbi.nlm.nih.gov/pubmed/28921815?tool=bestpractice.com[84]Costabile A, Bergillos-Meca T, Landriscina L, et al. An in vitro fermentation study on the effects of Gluten Friendly™ bread on microbiota and short chain fatty acids of fecal samples from healthy and celiac subjects. Front Microbiol. 2017 Sep 7;8:1722.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594085/http://www.ncbi.nlm.nih.gov/pubmed/28936206?tool=bestpractice.com[85]Mandile R, Picascia S, Parrella C, et al. Lack of immunogenicity of hydrolysed wheat flour in patients with coeliac disease after a short-term oral challenge. Aliment Pharmacol Ther. 2017 Aug;46(4):440-6.http://www.ncbi.nlm.nih.gov/pubmed/28627070?tool=bestpractice.com用微生物转谷氨酰胺酶处理小麦粉是另一种正在研究的方法。[86]Marino M, Casale R, Borghini R, et al. The effects of modified versus unmodified wheat gluten administration in patients with celiac disease. Int Immunopharmacol. 2017 Jun;47:1-8.http://www.ncbi.nlm.nih.gov/pubmed/28343108?tool=bestpractice.com
孟鲁司特
一项探索性研究表明，孟鲁司特（一种用于治疗哮喘的白三烯受体拮抗剂）可抑制上皮内淋巴细胞产生炎症介质，并可能加速黏膜愈合。[87]Kupfer S, Mayassi T, Setia N, et al. Su1166: a randomized, placebo-controlled pilot study of montelukast in celiac disease. Gastroenterology. 2018 May;154(6):S-491.
