Editing Ulcerative colitis (section)

==Research==
[[Helminthic therapy]] using the [[whipworm]] ''Trichuris suis'' has been shown in a [[randomized control trial]] from Iowa to show benefit in people with ulcerative colitis.<ref name="Trichuris suis therapy">{{cite journal | vauthors = Summers RW, Elliott DE, Urban JF, Thompson RA, Weinstock JV | title = Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial | journal = Gastroenterology | volume = 128 | issue = 4 | pages = 825–832 | date = April 2005 | pmid = 15825065 | doi = 10.1053/j.gastro.2005.01.005 | doi-access = free }}</ref> The therapy tests the [[hygiene hypothesis]] which argues that the absence of [[helminths]] in the colons of people in the developed world may lead to inflammation. Both helminthic therapy and fecal microbiota transplant induce a characteristic [[Th2]] white cell response in the diseased areas, which was unexpected given that ulcerative colitis was thought to involve Th2 overproduction.<ref name="Trichuris suis therapy"/>

[[Alicaforsen]] is a first generation antisense oligodeoxynucleotide designed to bind specifically to the human [[ICAM-1]] messenger [[RNA]] through Watson-Crick base pair interactions in order to subdue expression of ICAM-1.<ref name="Bennett CF, Condon TC, Grimm S, Chan H, Chiang MY 1994 3530–40">{{cite journal|vauthors=Bennett CF, Condon TC, Grimm S, Chan H, Chiang MY |title=Inhibition of endothelial cell-leukocyte adhesion molecule expression with antisense oligonucleotides |journal=The Journal of Immunology |volume=152 |issue=1 |pages=3530–40 |year=1994 |doi=10.4049/jimmunol.152.7.3530 |s2cid=34563008 }}</ref> ICAM-1 propagates an inflammatory response promoting the extravasation and activation of [[leukocytes]] (white blood cells) into inflamed tissue.<ref name="Bennett CF, Condon TC, Grimm S, Chan H, Chiang MY 1994 3530–40"/> Increased expression of ICAM-1 has been observed within the [[inflamed]] intestinal mucosa of ulcerative colitis patients, where ICAM-1 over production correlated with disease activity.<ref>{{cite journal | vauthors = Jones SC, Banks RE, Haidar A, Gearing AJ, Hemingway IK, Ibbotson SH, Dixon MF, Axon AT | title = Adhesion molecules in inflammatory bowel disease | journal = Gut | volume = 36 | issue = 5 | pages = 724–730 | date = May 1995 | pmid = 7541009 | pmc = 1382677 | doi = 10.1136/gut.36.5.724 }}</ref> This suggests that ICAM-1 is a potential therapeutic target in the treatment of ulcerative colitis.<ref>{{cite journal | vauthors = van Deventer SJ, Wedel MK, Baker BF, Xia S, Chuang E, Miner PB | title = A phase II dose ranging, double-blind, placebo-controlled study of alicaforsen enema in subjects with acute exacerbation of mild to moderate left-sided ulcerative colitis | journal = Alimentary Pharmacology & Therapeutics | volume = 23 | issue = 10 | pages = 1415–1425 | date = May 2006 | pmid = 16669956 | doi = 10.1111/j.1365-2036.2006.02910.x | s2cid = 31495688 | doi-access = free }}</ref>

Gram positive bacteria present in the lumen could be associated with extending the time of relapse for ulcerative colitis.<ref name=Ghouri2014>{{cite journal | vauthors = Ghouri YA, Richards DM, Rahimi EF, Krill JT, Jelinek KA, DuPont AW | title = Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease | journal = Clinical and Experimental Gastroenterology | volume = 7 | pages = 473–487 | date = 9 December 2014 | pmid = 25525379 | pmc = 4266241 | doi = 10.2147/CEG.S27530 | doi-access = free }}</ref>

A series of drugs in development looks to disrupt the inflammation process by selectively targeting an [[ion channel]] in the inflammation signaling cascade known as KCa3.1.<ref name="Strøbæk, D. 2013">{{cite journal | vauthors = Strøbæk D, Brown DT, Jenkins DP, Chen YJ, Coleman N, Ando Y, Chiu P, Jørgensen S, Demnitz J, Wulff H, Christophersen P | title = NS6180, a new K(Ca) 3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease | journal = British Journal of Pharmacology | volume = 168 | issue = 2 | pages = 432–444 | date = January 2013 | pmid = 22891655 | pmc = 3572569 | doi = 10.1111/j.1476-5381.2012.02143.x }}</ref> In a preclinical study in rats and mice, inhibition of KCa3.1 disrupted the production of Th1 cytokines IL-2 and TNF-α and decreased colon inflammation as effectively as [[sulfasalazine]].<ref name="Strøbæk, D. 2013"/>

Neutrophil extracellular traps<ref name=Bennike>{{cite journal | vauthors = Bennike TB, Carlsen TG, Ellingsen T, Bonderup OK, Glerup H, Bøgsted M, Christiansen G, Birkelund S, Stensballe A, Andersen V | title = Neutrophil Extracellular Traps in Ulcerative Colitis: A Proteome Analysis of Intestinal Biopsies | journal = Inflammatory Bowel Diseases | volume = 21 | issue = 9 | pages = 2052–2067 | date = September 2015 | pmid = 25993694 | pmc = 4603666 | doi = 10.1097/MIB.0000000000000460 }}</ref> and the resulting degradation of the extracellular matrix<ref>{{cite journal | vauthors = Kirov S, Sasson A, Zhang C, Chasalow S, Dongre A, Steen H, Stensballe A, Andersen V, Birkelund S, Bennike TB | title = Degradation of the extracellular matrix is part of the pathology of ulcerative colitis | journal = Molecular Omics | volume = 15 | issue = 1 | pages = 67–76 | date = February 2019 | pmid = 30702115 | doi = 10.1039/C8MO00239H | doi-access = free }}</ref> have been reported in the colon mucosa in ulcerative colitis patients in clinical remission, indicating the involvement of the innate immune system in the etiology.<ref name=Bennike />

[[Fexofenadine]], an antihistamine drug used in treatment of allergies, has shown promise in a combination therapy in some studies.<ref>{{cite journal | vauthors = Raithel M, Winterkamp S, Weidenhiller M, Müller S, Hahn EG | title = Combination therapy using fexofenadine, disodium cromoglycate, and a hypoallergenic amino acid-based formula induced remission in a patient with steroid-dependent, chronically active ulcerative colitis | journal = International Journal of Colorectal Disease | volume = 22 | issue = 7 | pages = 833–839 | date = July 2007 | pmid = 16944185 | doi = 10.1007/s00384-006-0120-y | s2cid = 2605447 }}</ref><ref name=Gautam>{{cite journal | vauthors = Dhaneshwar S, Gautam H | title = Exploring novel colon-targeting antihistaminic prodrug for colitis | journal = Journal of Physiology and Pharmacology | volume = 63 | issue = 4 | pages = 327–337 | date = August 2012 | pmid = 23070081 |url=http://www.jpp.krakow.pl/journal/archive/08_12/pdf/327_08_12_article.pdf }}</ref> Opportunely, low gastrointestinal absorption (or high absorbed drug gastrointestinal secretion) of fexofenadine results in higher concentration at the site of inflammation. Thus, the drug may locally decrease histamine secretion by involved gastrointestinal mast cells and alleviate the inflammation.<ref name=Gautam />

There is evidence that [[etrolizumab]] is effective for ulcerative colitis, with phase 3 trials underway as of 2016.<ref name=Hir2015/><ref>{{cite journal | vauthors = Vermeire S, O'Byrne S, Keir M, Williams M, Lu TT, Mansfield JC, Lamb CA, Feagan BG, Panes J, Salas A, Baumgart DC, Schreiber S, Dotan I, Sandborn WJ, Tew GW, Luca D, Tang MT, Diehl L, Eastham-Anderson J, De Hertogh G, Perrier C, Egen JG, Kirby JA, van Assche G, Rutgeerts P | title = Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial | journal = Lancet | volume = 384 | issue = 9940 | pages = 309–318 | date = July 2014 | pmid = 24814090 | doi = 10.1016/S0140-6736(14)60661-9 | s2cid = 7369482 | doi-access = free }}</ref><ref name=":6">{{cite journal | vauthors = Rosenfeld G, Parker CE, MacDonald JK, Bressler B | title = Etrolizumab for induction of remission in ulcerative colitis | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 12 | pages = CD011661 | date = December 2015 | pmid = 26630451 | pmc = 8612697 | doi = 10.1002/14651858.CD011661.pub2 }}</ref><ref>{{cite journal | vauthors = Makker J, Hommes DW | title = Etrolizumab for ulcerative colitis: the new kid on the block? | journal = Expert Opinion on Biological Therapy | volume = 16 | issue = 4 | pages = 567–572 | date = 2016 | pmid = 26914639 | doi = 10.1517/14712598.2016.1158807 | s2cid = 24706213 }}</ref> Etrolizumab is a humanized monoclonal antibody that targets the β7 subunit of integrins α4β7 and αEβ7, ultimately blocking migration and retention of leukocytes in the intestinal mucosa.<ref name=":6" /> As of early 2022, [[Roche]] halted clinical trials for the use of etrolizumab in the treatment of ulcerative colitis.<ref>{{cite web |last=Taylor |first=Nick |date=3 February 2022 |title=Roche lets go of etro, dumping phase 3 Crohn's prospect 18 months after posting weak colitis data |url=https://www.fiercebiotech.com/biotech/roche-lets-go-etro-dumping-phase-3-crohn-s-prospect-18-months-after-posting-weak-colitis |access-date=12 December 2023 |website=Fierce Biotech}}</ref>

A type of [[leukocyte apheresis]], known as granulocyte and monocyte adsorptive apheresis, still requires large-scale trials to determine whether or not it is effective.<ref>{{cite journal | vauthors = Abreu MT, Plevy S, Sands BE, Weinstein R | title = Selective leukocyte apheresis for the treatment of inflammatory bowel disease | journal = Journal of Clinical Gastroenterology | volume = 41 | issue = 10 | pages = 874–888 | date = 2007 | pmid = 18090155 | doi = 10.1097/MCG.0b013e3180479435 | s2cid = 36724094 }}</ref> Results from small trials have been tentatively positive.<ref>{{cite journal | vauthors = Vernia P, D'Ovidio V, Meo D | title = Leukocytapheresis in the treatment of inflammatory bowel disease: Current position and perspectives | journal = Transfusion and Apheresis Science | volume = 43 | issue = 2 | pages = 227–229 | date = October 2010 | pmid = 20817610 | doi = 10.1016/j.transci.2010.07.023 }}</ref>