{"id":10113,"date":"2016-09-25T07:44:30","date_gmt":"2016-09-25T07:44:30","guid":{"rendered":"http:\/\/revoscience.com\/en\/?p=10113"},"modified":"2016-09-25T07:44:30","modified_gmt":"2016-09-25T07:44:30","slug":"new-therapeutic-target-for-crohns-disease","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/new-therapeutic-target-for-crohns-disease\/","title":{"rendered":"New Therapeutic Target for Crohn’s Disease"},"content":{"rendered":"
\"As<\/a>
As IBD worsens, levels of the gene regulator EZH2 increase, lowering numbers of protector cells. Source: SBP<\/figcaption><\/figure>\n

Research from the Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies a promising new target for future drugs to treat inflammatory bowel disease (IBD). The study, published in\u00a0Cell Reports<\/em>, also indicates that another protein, protein kinase C (PKC) \u03bb\/\u03b9, may serve as a biomarker of IBD severity.<\/span><\/p>\n

\u201cThe intestine is protected by specialized cells, called Paneth cells, that secrete antimicrobial peptides,\u201d said Jorge Moscat, Ph.D., deputy director and professor in the NCI-designated Cancer Center and senior author of the paper. \u201cWe found that maintaining normal numbers of Paneth cells requires PKC \u03bb\/\u03b9, and that the amount of PKC \u03bb\/\u03b9 decreases as IBD gets worse. We also discovered a way to prevent Paneth cell loss\u2014inhibiting a protein called EZH2, which could be a new therapeutic strategy for IBD.\u201d<\/span><\/p>\n

[pullquote]The team verified the relevance of their findings in intestinal biopsy samples from 30 patients with Crohn\u2019s disease.[\/pullquote]<\/p>\n

IBD, which includes Crohn\u2019s disease and ulcerative colitis, affects 1.4 million people in the U.S. These chronic conditions are often debilitating, as they cause unpredictable abdominal pain and diarrhea. Because current medications only help control symptoms and not the underlying disease, 70% of Crohn\u2019s patients and 30% of those with colitis must eventually undergo surgery. In addition, IBD increases risk of intestinal cancer by as much as 60%.<\/span><\/p>\n

\u201cWe also examined the effect of PKC \u03bb\/\u03b9 on tumor formation,\u201d said Maria Diaz-Meco, Ph.D., also a professor in the Cancer Center and co-author of the paper. \u201cIn contrast to some previous studies indicating that it might promote cancer development, we demonstrate that in the intestine, PKC \u03bb\/\u03b9 is protective.\u201d<\/span><\/p>\n

\u201cWe inactivated the PKC \u03bb\/\u03b9 gene in the intestine of mice, which caused them to have very few Paneth cells,\u201d added Diaz-Meco. \u201cWithout Paneth cells, the intestine is more susceptible to bacterial infiltration, which leads to inflammation. Since inflammation favors cancer, it makes sense that PKC \u03bb\/\u03b9 is a tumor suppressor in this setting.\u201d<\/span><\/p>\n

To find a way to boost Paneth cell numbers and possibly treat IBD, the team looked for what drives the deficit in these protector cells. The key link was overactive EZH2, which turns off genes needed to generate Paneth cells.<\/span><\/p>\n

\u201cWe used an\u00a0in vitro<\/em>\u00a0model\u2014\u2018mini guts\u2019 in a dish\u2014to show that blocking EZH2 helps return the number of Paneth cells to normal,\u201d said Yuki Nakanishi, M.D., a postdoctoral fellow in the Moscat\/ Diaz-Meco lab and lead author of the work. \u201cThis demonstrates that inhibiting EZH2 could be a new way to slow the progression of IBD.\u201d<\/span><\/p>\n

Importantly, the team verified the relevance of their findings in intestinal biopsy samples from 30 patients with Crohn\u2019s disease. Disease progression correlated with lower levels of PKC \u03bb\/\u03b9.<\/span><\/p>\n

\u201cEZH2 inhibitors are currently being developed by the pharmaceutical industry to treat other cancers, so they could be tested for IBD relatively soon,\u201d said Moscat. \u201cBut first, we need to do preclinical studies to test whether they block progression of the disease.\u201d<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

\u201cThe intestine is protected by specialized cells, called Paneth cells, that secrete antimicrobial peptides,\u201d said Jorge Moscat, Ph.D., deputy director and professor in the NCI-designated Cancer Center and senior author of the paper. \u201cWe found that maintaining normal numbers of Paneth cells requires PKC \u03bb\/\u03b9, and that the amount of PKC \u03bb\/\u03b9 decreases as IBD gets worse. We also discovered a way to prevent Paneth cell loss\u2014inhibiting a protein called EZH2, which could be a new therapeutic strategy for IBD.\u201d<\/p>\n","protected":false},"author":6,"featured_media":10114,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26,17],"tags":[],"class_list":["post-10113","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicine","category-research"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",800,634,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford-150x150.jpeg",150,150,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford-300x237.jpeg",300,237,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",750,594,false],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",750,594,false],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",800,634,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",800,634,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",800,634,false],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",719,570,false],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",600,476,false],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",600,476,false],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",618,490,false],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",454,360,false],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",82,65,false],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",640,507,false],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",96,76,false],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2016\/09\/ddd1609_sanford.jpeg",150,119,false]},"author_info":{"info":["Amrita Tuladhar"]},"category_info":"Medicine<\/a> Research<\/a>","tag_info":"Research","comment_count":"0","_links":{"self":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/10113","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/comments?post=10113"}],"version-history":[{"count":0,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/10113\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media\/10114"}],"wp:attachment":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media?parent=10113"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/categories?post=10113"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/tags?post=10113"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}