Current Status of Medical Therapy for Inflammatory Bowel Disease: The Wealth of Medications

Nadpara, Neil; Reichenbach, Zachary Wilmer; Ehrlich, Adam C.; Friedenberg, Frank K.

doi:10.1007/s10620-020-06471-4

Cited by 13 publications

(4 citation statements)

References 70 publications

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“…How to manage these diseases efficaciously remains a problem. While diverse therapies for ameliorating the clinical symptoms of OLP and IBD are under development or in the clinic, long-term therapeutic efficacy continues to be a serious challenge [42][43][44].…”

Section: Discussionmentioning

confidence: 99%

ZFP36 promotes VDR mRNA degradation to facilitate cell death in oral and colonic epithelial cells

Wang

Cao

et al. 2021

Cell Commun Signal

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Background Vitamin D receptor (VDR) plays a vital protective role in oral and colonic epithelial cells. Albeit we know that VDR expression is reduced in the mucosal epithelial layers of autoimmune diseases, the mechanism by which VDR is decreased remains elusive. Methods VDR and zinc finger protein 36 (ZFP36) levels in human samples and cell lines were detected by real-time PCR, western blot and immunostaining. Luciferase report assay was used to test cis-elements in VDR gene promoter, real-time PCR was applied to measure mRNA decay and western blot was performed to evaluate protein degradation. RNA affinity chromatography assay was used to test protein-mRNA interaction. Co-immunoprecipitation was used to detect protein–protein interaction. The role of ZFP36 in AU-rich elements (AREs) in the 3′ untranslated region (UTR) of VDR mRNA was also measured by luciferase report assay. Results We identify ZFP36 can bind with the AREs in the 3’UTR of VDR mRNA, leading to mRNA degradation in oral and colonic epithelial cells under inflammatory circumstance. Either ZFP36 protein or AREs of VDR mRNA mutation abolishes this protein-mRNA binding process. After the key amino acid’s mutation, ZFP36 fails to decrease VDR mRNA expression. We also find that VDR physically binds with Y box-binding protein 1 (YBX-1) to block YBX-1’s nuclear translocation and ameliorate cell death in the presence of inflammation. Conclusion These findings provide insights into the cause of VDR decrease in oral and colonic epithelial cells under inflammatory condition and explain how VDR maintains cell viability in these cells.

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Section: Discussionmentioning

confidence: 99%

ZFP36 promotes VDR mRNA degradation to facilitate cell death in oral and colonic epithelial cells

Wang

Cao

et al. 2021

Cell Commun Signal

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“…The cause of IBD is not known but host genetic factors, microbiota, and environmental factors are believed to interact, leading to an adverse immune response in the GI tract. Treatment options for IBD include aminosalicylates, antibiotics, steroids, immunomodulators, stem cell therapies, and surgery [75][76][77]. However, none of these treatments are effective in all patients.…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%

Colostrum Therapy for Human Gastrointestinal Health and Disease

Chandwe

Kelly

2021

Nutrients

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There is increasing awareness that a broad range of gastrointestinal diseases, and some systemic diseases, are characterized by failure of the mucosal barrier. Bovine colostrum is a complex biological fluid replete with growth factors, nutrients, hormones, and paracrine factors which have a range of properties likely to contribute to mucosal healing in a wide range of infective, inflammatory, and injury conditions. In this review, we describe the anatomy and physiology of the intestinal barrier and how it may fail. We survey selected diseases in which disordered barrier function contributes to disease pathogenesis or progression, and review the evidence for or against efficacy of bovine colostrum in management. These disorders include enteropathy due to non-steroidal anti-inflammatory drugs (NSAIDs), inflammatory bowel disease (IBD), necrotizing enterocolitis, infectious diarrhea, intestinal failure, and damage due to cancer therapy. In animal models, bovine colostrum benefits NSAID enteropathy, IBD, and intestinal failure. In human trials, there is substantial evidence of efficacy of bovine colostrum in inflammatory bowel disease and in infectious diarrhea. Given the robust scientific rationale for using bovine colostrum as a promoter of mucosal healing, further work is needed to define its role in therapy.

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“…This unmet medical need in combination with a greater understanding of the pathological basis of IBD has led to an exponential rise in the number of compounds in clinical development for this disease over the last three decades. 12,13 Consequently, the number of IBD clinical trials being initiated continues to increase annually. Specifically, the number of CD clinical trials initiated each year more than doubled between 1999 and 2019 while the number of UC clinical trials increased 10fold during the same time period (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, there remains an unmet medical need in IBD. This unmet medical need in combination with a greater understanding of the pathological basis of IBD has led to an exponential rise in the number of compounds in clinical development for this disease over the last three decades 12,13 . Consequently, the number of IBD clinical trials being initiated continues to increase annually.…”

Section: Introductionmentioning

confidence: 99%

Review article: randomised controlled trials in inflammatory bowel disease—common challenges and potential solutions

Schreiber

Irving

Sharara

et al. 2022

Aliment Pharmacol Ther

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Background:Recruitment rates for Crohn's disease and ulcerative colitis clinical trials continue to decrease annually. The inability to reach recruitment targets and complete trials has serious implications for stakeholders in the inflammatory bowel disease (IBD) community. Action is required to ensure patients with an unmet medical need have access to new therapies to improve the management of their IBD. Aims: Identify challenges contributing to recruitment decline in IBD clinical trials and propose potential solutions. Methods: PubMed and Google were used to identify literature, regulatory guidelines and conference proceedings related to IBD clinical trials and related concepts. Data on IBD clinical trials conducted between 1989 and 2020 were extracted from the Trialtrove database.Results: Key aspects that may improve recruitment rates were identified. An increasingly patient-centric approach should be taken to study design including improvements to the readability of key trial documentation and inclusion of patient representatives in trial planning. Placebo is unappealing to patients; approaches including platform trials should be explored to minimise placebo exposure. Non-invasive imaging, biomarkers and novel digital endpoints should continue to be examined to reduce the burden on patients. Reducing the administrative burden associated with trials via the use of electronic signatures, for example, may benefit study sites and investigators.Changes implemented to IBD trials during the COVID-19 pandemic provided examples of how trial conduct can be rapidly and constructively adapted. Conclusions:To improve recruitment in Crohn's disease and ulcerative colitis trials, the IBD community should address a broad range of issues related to clinical trial conduct.

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Current Status of Medical Therapy for Inflammatory Bowel Disease: The Wealth of Medications

Cited by 13 publications

References 70 publications

ZFP36 promotes VDR mRNA degradation to facilitate cell death in oral and colonic epithelial cells

ZFP36 promotes VDR mRNA degradation to facilitate cell death in oral and colonic epithelial cells

Colostrum Therapy for Human Gastrointestinal Health and Disease

Review article: randomised controlled trials in inflammatory bowel disease—common challenges and potential solutions

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