Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Maximizing Treatment Options for IBD through Drug Repurposing

In Press, (this is not the final "Version of Record"). Available online 19 July, 2024
Author(s): Amir Hossein Barjasteh, Abdulridha Mohammed Al-Asady, Hanieh Latifi, Souad Al Okla, Nasser Al-Nazwani, Amir Avan, Majid Khazaei, Mikhail Ryzhikov, Hanieh Nadi-Yazdi and Seyed Mahdi Hassanian*
Published on: 19 July, 2024

DOI: 10.2174/0113816128318032240702045822

Price: $95

Abstract

Chronic inflammation characterizes Inflammatory Bowel Disease (IBD), encompassing Crohn's Disease (CD) and Ulcerative Colitis (UC). Despite modest activity of disease in most UC patients, exacerbations occur, especially in those with severe symptoms, necessitating interventions, like colectomy. Current treatments for IBD, predominantly small molecule therapies, impose significant economic burdens. Drug repurposing offers a cost-effective alternative, leveraging existing drugs for novel therapeutic applications. This approach capitalizes on shared molecular pathways across diseases, accelerating therapeutic discovery while minimizing costs and risks. This article provides an overview of IBD and explores drug repurposing as a promising avenue for more effective and affordable treatments. Through computational and animal studies, potential drug candidates are categorized, offering insights into IBD pathogenesis and treatment strategies.

[1]
Ponder A, Long MD. A clinical review of recent findings in the epidemiology of inflammatory bowel disease. Clin Epidemiol 2013; 5: 237-47.
[PMID: 23922506]
[2]
Cosnes J, Gower–Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 2011; 140(6): 1785-94.
[http://dx.doi.org/10.1053/j.gastro.2011.01.055]
[3]
Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies. Lancet 2017; 390(10114): 2769-78.
[http://dx.doi.org/10.1016/S0140-6736(17)32448-0] [PMID: 29050646]
[4]
Burri E, Maillard MH, Schoepfer AM, et al. Treatment algorithm for mild and moderate-to-severe ulcerative colitis: An update. Digestion 2020; 101 (Suppl. 1): 2-15.
[http://dx.doi.org/10.1159/000504092] [PMID: 31945767]
[5]
Truelove SC, Witts LJ. Cortisone in ulcerative colitis; Preliminary report on a therapeutic trial. BMJ 1954; 2(4884): 375-8.
[http://dx.doi.org/10.1136/bmj.2.4884.375] [PMID: 13182220]
[6]
Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 1987; 317(26): 1625-9.
[http://dx.doi.org/10.1056/NEJM198712243172603] [PMID: 3317057]
[7]
Sturm A, Maaser C, Calabrese E, et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 2: IBD scores and general principles and technical aspects. J Crohn’s Colitis 2019; 13(3): 273-84.
[http://dx.doi.org/10.1093/ecco-jcc/jjy114] [PMID: 30137278]
[8]
Cichewicz A, Tencer T, Gupte-Singh K, Egodage S, Burnett H, Kumar J. A systematic review of the economic and health-related quality of life impact of advanced therapies used to treat moderate-to-severe ulcerative colitis. Adv Ther 2023; 40(5): 2116-46.
[http://dx.doi.org/10.1007/s12325-023-02488-z] [PMID: 37000363]
[9]
Jostins L, Ripke S, Weersma RK, et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491(7422): 119-24.
[http://dx.doi.org/10.1038/nature11582] [PMID: 23128233]
[10]
Lee HS, Cleynen I. Molecular profiling of inflammatory bowel disease: Is it ready for use in clinical decision-making? Cells 2019; 8(6): 535.
[http://dx.doi.org/10.3390/cells8060535] [PMID: 31167397]
[11]
Porter RJ, Kalla R, Ho GT. Ulcerative colitis: Recent advances in the understanding of disease pathogenesis. F1000 Res 2020; 9: 294.
[http://dx.doi.org/10.12688/f1000research.20805.1] [PMID: 32399194]
[12]
Kaplan GG, Ng SC. Understanding and preventing the global increase of inflammatory bowel disease. Gastroenterology 2017; 152(2): 313-321.e2.
[http://dx.doi.org/10.1053/j.gastro.2016.10.020] [PMID: 27793607]
[13]
Kirsner JB. Historical aspects of inflammatory bowel disease. J Clin Gastroenterol 1988; 10(3): 286-97.
[http://dx.doi.org/10.1097/00004836-198806000-00012] [PMID: 2980764]
[14]
Sheikh SZ, Hegazi RA, Kobayashi T, Onyiah JC, Russo SM, Matsuoka K. An anti-inflammatory role for carbon monoxide and heme oxygenase-1 in chronic Th2-mediated murine colitis. J Immunol 2011; 186(9): 5506-13.
[http://dx.doi.org/10.4049/jimmunol.1002433]
[15]
Nyboe Andersen N, Gørtz S, Frisch M, Jess T. Reduced risk of UC in families affected by appendicitis: A Danish national cohort study. Gut 2017; 66(8): 1398-402.
[http://dx.doi.org/10.1136/gutjnl-2015-311131] [PMID: 27196591]
[16]
John S, Luben R, Shrestha SS, Welch A, Khaw KT, Hart AR. Dietary n-3 polyunsaturated fatty acids and the aetiology of ulcerative colitis: A UK prospective cohort study. Eur J Gastroenterol Hepatol 2010; 22(5): 602-6.
[http://dx.doi.org/10.1097/MEG.0b013e3283352d05] [PMID: 20216220]
[17]
Amarapurkar AD, Amarapurkar DN, Rathi P, et al. Risk factors for inflammatory bowel disease: A prospective multi-center study. Indian J Gastroenterol 2018; 37(3): 189-95.
[http://dx.doi.org/10.1007/s12664-018-0850-0] [PMID: 29987750]
[18]
Jantchou P, Morois S, Clavel-Chapelon F, Boutron-Ruault MC, Carbonnel F. Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study. Am J Gastroenterol 2010; 105(10): 2195-201.
[http://dx.doi.org/10.1038/ajg.2010.192] [PMID: 20461067]
[19]
McCauley HA, Guasch G. Three cheers for the goblet cell: Maintaining homeostasis in mucosal epithelia. Trends Mol Med 2015; 21(8): 492-503.
[http://dx.doi.org/10.1016/j.molmed.2015.06.003] [PMID: 26144290]
[20]
Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9(11): 799-809.
[http://dx.doi.org/10.1038/nri2653] [PMID: 19855405]
[21]
Cattin AL, Le Beyec J, Barreau F, et al. Hepatocyte nuclear factor 4alpha, a key factor for homeostasis, cell architecture, and barrier function of the adult intestinal epithelium. Mol Cell Biol 2009; 29(23): 6294-308.
[http://dx.doi.org/10.1128/MCB.00939-09] [PMID: 19805521]
[22]
Asano K, Matsushita T, Umeno J, et al. A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. Nat Genet 2009; 41(12): 1325-9.
[http://dx.doi.org/10.1038/ng.482] [PMID: 19915573]
[23]
McGovern DPB, Gardet A, Törkvist L, et al. Genome-wide association identifies multiple ulcerative colitis susceptibility loci. Nat Genet 2010; 42(4): 332-7.
[http://dx.doi.org/10.1038/ng.549] [PMID: 20228799]
[24]
Heller F, Fromm A, Gitter AH, Mankertz J, Schulzke J-D. Epithelial apoptosis is a prominent feature of the epithelial barrier disturbance in intestinal inflammation: Effect of pro-inflammatory interleukin-13 on epithelial cell function. Mucosal Immunol 2008; 1 (Suppl. 1): S58-61.
[http://dx.doi.org/10.1038/mi.2008.46] [PMID: 19079233]
[25]
Watson CJ, Hoare CJ, Garrod DR, Carlson GL, Warhurst G. Interferon-γ selectively increases epithelial permeability to large molecules by activating different populations of paracellular pores. J Cell Sci 2005; 118(22): 5221-30.
[http://dx.doi.org/10.1242/jcs.02630] [PMID: 16249235]
[26]
Hallert C, Björck I, Nyman M, Pousette A, Grännö C, Svensson H. Increasing fecal butyrate in ulcerative colitis patients by diet: Controlled pilot study. Inflamm Bowel Dis 2003; 9(2): 116-21.
[http://dx.doi.org/10.1097/00054725-200303000-00005] [PMID: 12769445]
[27]
Park S, Abdi T, Gentry M, Laine L. Histological disease activity as a predictor of clinical relapse among patients with ulcerative colitis: Systematic review and meta-analysis. Am J Gastroenterol 2016; 111(12): 1692-701.
[http://dx.doi.org/10.1038/ajg.2016.418] [PMID: 27725645]
[28]
Lin N, Simon MC. Hypoxia-inducible factors: Key regulators of myeloid cells during inflammation. J Clin Invest 2016; 126(10): 3661-71.
[http://dx.doi.org/10.1172/JCI84426] [PMID: 27599290]
[29]
Taylor CT, Colgan SP. Regulation of immunity and inflammation by hypoxia in immunological niches. Nat Rev Immunol 2017; 17(12): 774-85.
[http://dx.doi.org/10.1038/nri.2017.103] [PMID: 28972206]
[30]
Angelidou I, Chrysanthopoulou A, Mitsios A, Arelaki S, Arampatzioglou A, Kambas K. REDD1/autophagy pathway is associated with neutrophil-driven IL-1β inflammatory response in active ulcerative colitis. J Immunol 2018; 200(12): 3950-61.
[31]
Dinallo V, Marafini I, Di Fusco D, et al. Neutrophil extracellular traps sustain inflammatory signals in ulcerative colitis. J Crohn’s Colitis 2019; 13(6): 772-84.
[http://dx.doi.org/10.1093/ecco-jcc/jjy215] [PMID: 30715224]
[32]
Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 2003; 3(7): 521-33.
[http://dx.doi.org/10.1038/nri1132] [PMID: 12876555]
[33]
Fuss IJ, Heller F, Boirivant M, et al. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest 2004; 113(10): 1490-7.
[http://dx.doi.org/10.1172/JCI19836] [PMID: 15146247]
[34]
Kobayashi T, Okamoto S, Hisamatsu T, et al. IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn’s disease. Gut 2008; 57(12): 1682-9.
[http://dx.doi.org/10.1136/gut.2007.135053] [PMID: 18653729]
[35]
Nalleweg N, Chiriac MT, Podstawa E, et al. IL-9 and its receptor are predominantly involved in the pathogenesis of UC. Gut 2015; 64(5): 743-55.
[http://dx.doi.org/10.1136/gutjnl-2013-305947] [PMID: 24957265]
[36]
Duerr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006; 314(5804): 1461-3.
[http://dx.doi.org/10.1126/science.1135245] [PMID: 17068223]
[37]
Teng MWL, Bowman EP, McElwee JJ, et al. IL-12 and IL-23 cytokines: From discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med 2015; 21(7): 719-29.
[http://dx.doi.org/10.1038/nm.3895] [PMID: 26121196]
[38]
Wheat CL, Ko CW, Clark-Snustad K, Grembowski D, Thornton TA, Devine B. Inflammatory Bowel Disease (IBD) pharmacotherapy and the risk of serious infection: A systematic review and network meta-analysis. BMC Gastroenterol 2017; 17(1): 52.
[http://dx.doi.org/10.1186/s12876-017-0602-0] [PMID: 28407755]
[39]
Zurba Y, Gros B, Shehab M. Exploring the pipeline of novel therapies for inflammatory bowel disease; state of the art review. Biomedicines 2023; 11(3): 747.
[http://dx.doi.org/10.3390/biomedicines11030747] [PMID: 36979724]
[40]
Altaf-Ul-Amin M. Drug repurposing for inflammatory bowel disease based on relations among drugs, diseases and genes. J Gastro Hepato 2023; 9(17): 1-8.
[41]
Sadegh S, Matschinske J, Blumenthal DB, et al. Exploring the SARS-CoV-2 virus-host-drug interactome for drug repurposing. Nat Commun 2020; 11(1): 3518.
[http://dx.doi.org/10.1038/s41467-020-17189-2] [PMID: 32665542]
[42]
Kitani T, Maddipatla SC, Madupuri R, et al. In search of newer targets for inflammatory bowel disease: A systems and a network medicine approach. Netw Syst Med 2021; 4(1): 74-87.
[http://dx.doi.org/10.1089/nsm.2020.0012]
[43]
Dudley JT, Sirota M, Shenoy M, et al. Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease. Sci Transl Med 2011; 3(96): 96ra76.
[http://dx.doi.org/10.1126/scitranslmed.3002648] [PMID: 21849664]
[44]
Sadegh S, Skelton J, Anastasi E, et al. Network medicine for disease module identification and drug repurposing with the NeDRex platform. Nat Commun 2021; 12(1): 6848.
[http://dx.doi.org/10.1038/s41467-021-27138-2] [PMID: 34824199]
[45]
Grenier L, Hu P. Computational drug repurposing for inflammatory bowel disease using genetic information. Comput Struct Biotechnol J 2019; 17: 127-35.
[http://dx.doi.org/10.1016/j.csbj.2019.01.001] [PMID: 30728920]
[46]
Nitzan O, Elias M, Peretz A, Saliba W. Role of antibiotics for treatment of inflammatory bowel disease. World J Gastroenterol 2016; 22(3): 1078-87.
[http://dx.doi.org/10.3748/wjg.v22.i3.1078] [PMID: 26811648]
[47]
Tian R, Li Y, Wang X, et al. A pharmacoinformatics analysis of artemisinin targets and de novo design of hits for treating ulcerative colitis. Front Pharmacol 2022; 13: 843043.
[http://dx.doi.org/10.3389/fphar.2022.843043] [PMID: 35370688]
[48]
Johnson TO, Akinsanmi AO, Ejembi SA, et al. Modern drug discovery for inflammatory bowel disease: The role of computational methods. World J Gastroenterol 2023; 29(2): 310-31.
[http://dx.doi.org/10.3748/wjg.v29.i2.310] [PMID: 36687123]
[49]
Can G, Ayvaz S, Can H, et al. The syk inhibitor fostamatinib decreases the severity of colonic mucosal damage in a rodent model of colitis. J Crohn’s Colitis 2015; 9(10): 907-17.
[http://dx.doi.org/10.1093/ecco-jcc/jjv114] [PMID: 26116555]
[50]
El-Mahdy NA, El-Sayad MES, El-Kadem AH, Abu-Risha SELS. Metformin alleviates inflammation in oxazolone induced ulcerative colitis in rats: Plausible role of sphingosine kinase 1/sphingosine 1 phosphate signaling pathway. Immunopharmacol Immunotoxicol 2021; 43(2): 192-202.
[http://dx.doi.org/10.1080/08923973.2021.1878214] [PMID: 33504231]
[51]
Koh SJ, Kim JM, Kim IK, Ko SH, Kim JS. Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer. J Gastroenterol Hepatol 2014; 29(3): 502-10.
[http://dx.doi.org/10.1111/jgh.12435] [PMID: 24716225]
[52]
Liu X, Sun Z, Wang H. Metformin alleviates experimental colitis in mice by up-regulating TGF-β signaling. Biotech Histochem 2021; 96(2): 146-52.
[http://dx.doi.org/10.1080/10520295.2020.1776896] [PMID: 32654569]
[53]
Ali FEM, M Elfiky M, Fadda WA, et al. Regulation of IL-6/STAT-3/Wnt axis by nifuroxazide dampens colon ulcer in acetic acid-induced ulcerative colitis model: Novel mechanistic insight. Life Sci 2021; 276: 119433.
[http://dx.doi.org/10.1016/j.lfs.2021.119433] [PMID: 33794250]
[54]
Chumanevich AA, Witalison EE, Chaparala A, et al. Repurposing the anti-malarial drug, quinacrine: New anti-colitis properties. Oncotarget 2016; 7(33): 52928-39.
[http://dx.doi.org/10.18632/oncotarget.10608] [PMID: 27447967]
[55]
Byrnes JJ, Gross S, Ellard C, Connolly K, Donahue S, Picarella D. Effects of the ACE2 inhibitor GL1001 on acute dextran sodium sulfate-induced colitis in mice. Inflamm Res 2009; 58(11): 819-27.
[http://dx.doi.org/10.1007/s00011-009-0053-3]
[56]
Chande N, MacDonald JK, Wang JJ, McDonald JWD. Unfractionated or low molecular weight heparin for induction of remission in ulcerative colitis: A cochrane inflammatory bowel disease and functional bowel disorders systematic review of randomized trials. Inflamm Bowel Dis 2011; 17(9): 1979-86.
[http://dx.doi.org/10.1002/ibd.21776] [PMID: 21618363]
[57]
Fairbrass KM, Hoshen D, Gracie DJ, Ford AC. Effect of ACE inhibitors and angiotensin II receptor blockers on disease outcomes in inflammatory bowel disease. Gut 2021; 70(1): 218.2-9.
[http://dx.doi.org/10.1136/gutjnl-2020-321186] [PMID: 32241900]
[58]
Jacobs JD, Wagner T, Gulotta G, et al. Impact of angiotensin II signaling blockade on clinical outcomes in patients with inflammatory bowel disease. Dig Dis Sci 2019; 64(7): 1938-44.
[http://dx.doi.org/10.1007/s10620-019-5474-4] [PMID: 30725290]
[59]
Shakibfar S, Allin K, Jess T, et al. Drug repurposing in Crohn’s disease using Danish Real-World Data. Pragmat Obs Res 2024; 15: 17-29.
[http://dx.doi.org/10.2147/POR.S444569] [PMID: 38404739]
[60]
Azuma K, Osaki T, Kurozumi S, et al. Anti-inflammatory effects of orally administered glucosamine oligomer in an experimental model of inflammatory bowel disease. Carbohydr Polym 2015; 115: 448-56.
[http://dx.doi.org/10.1016/j.carbpol.2014.09.012] [PMID: 25439918]
[61]
Jadav PD, Patel SH, Rachchh MA. Evaluation of anti-inflammatory effect of anti-platelet agent-clopidogrel in experimentally induced inflammatory bowel disease. Indian J Pharmacol 2012; 44(6): 744-8.
[http://dx.doi.org/10.4103/0253-7613.103278] [PMID: 23248405]
[62]
Ghorbanzadeh B, Behmanesh MA, Mahmoudinejad R, Zamaniyan M, Ekhtiar S, Paridar Y. The effect of montelukast, a leukotriene receptor antagonist, on the acetic acid-induced model of colitis in rats: Involvement of NO-cGMP-KATP channels pathway. Front Pharmacol 2022; 13: 1011141.
[http://dx.doi.org/10.3389/fphar.2022.1011141] [PMID: 36225573]
[63]
Guo W, Chen S, Li C, Xu J, Wang L. Application of disulfiram and its metabolites in treatment of inflammatory disorders. Front Pharmacol 2022; 12: 795078.
[http://dx.doi.org/10.3389/fphar.2021.795078] [PMID: 35185542]
[64]
Zhou W, Zhang H, Huang L, et al. Disulfiram with Cu2+ alleviates dextran sulfate sodium-induced ulcerative colitis in mice. Theranostics 2023; 13(9): 2879-95.
[http://dx.doi.org/10.7150/thno.81571] [PMID: 37284442]
[65]
Bhat MA, Roy S, Dhaneshwar S, Kumar S, Saxena SK. Desloratadine via its anti-inflammatory and antioxidative properties ameliorates TNBS-induced experimental colitis in rats. Immunopharmacol Immunotoxicol 2024; 2024: 1-14.
[http://dx.doi.org/10.1080/08923973.2024.2360043] [PMID: 38816915]
[66]
Eskandari M, Asgharzadeh F, Askarnia-faal MM, et al. Mebendazole, an anti-helminth drug, suppresses inflammation, oxidative stress and injury in a mouse model of ulcerative colitis. Sci Rep 2022; 12(1): 10249.
[http://dx.doi.org/10.1038/s41598-022-14420-6] [PMID: 35715495]
[67]
Pena Rossi C, Hanauer SB, Tomasevic R, Hunter JO, Shafran I, Graffner H. Interferon beta-1a for the maintenance of remission in patients with Crohn’s disease: Results of a phase II dose-finding study. BMC Gastroenterol 2009; 9(1): 22.
[http://dx.doi.org/10.1186/1471-230X-9-22] [PMID: 19302707]
[68]
Ardesia M, Ferlazzo G, Fries W. Vitamin D and inflammatory bowel disease. BioMed Res Int 2015; 2015: 1-16.
[http://dx.doi.org/10.1155/2015/470805] [PMID: 26000293]
[69]
Bramuzzo M, Ventura A, Martelossi S, Lazzerini M. Thalidomide for inflammatory bowel disease. Medicine 2016; 95(30): e4239.
[http://dx.doi.org/10.1097/MD.0000000000004239] [PMID: 27472695]
[70]
Bai L, Scott MKD, Steinberg E, et al. Computational drug repositioning of atorvastatin for ulcerative colitis. J Am Med Inform Assoc 2021; 28(11): 2325-35.
[http://dx.doi.org/10.1093/jamia/ocab165] [PMID: 34529084]
[71]
Grip O, Janciauskiene S, Bredberg A. Use of atorvastatin as an anti‐inflammatory treatment in Crohn’s disease. Br J Pharmacol 2008; 155(7): 1085-92.
[http://dx.doi.org/10.1038/bjp.2008.369] [PMID: 18806816]
[72]
Lund JL, Stürmer T, Porter CQ, Sandler RS, Kappelman MD. Thiazolidinedione use and ulcerative colitis-related flares: An exploratory analysis of administrative data. Inflamm Bowel Dis 2011; 17(3): 787-94.
[http://dx.doi.org/10.1002/ibd.21348] [PMID: 20848530]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy