Maximizing Treatment Options for IBD through Drug Repurposing


Cite item

Full Text

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.

About the authors

Amir Barjasteh

Faculty of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Abdulridha Al-Asady

Department of Medical Sciences, Faculty of Nursing,, Warith Al-Anbiyaa University

Email: info@benthamscience.net

Hanieh Latifi

Faculty of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Souad Al Okla

College of Medicine and Health Sciences, National University of Science and Technology

Email: info@benthamscience.net

Nasser Al-Nazwani

Department of Biochemistry, College of Medicine and Health Sciences,, National University of Science and Technology

Email: info@benthamscience.net

Amir Avan

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences,

Email: info@benthamscience.net

Majid Khazaei

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Mikhail Ryzhikov

School of Medicine, Saint Louis University

Email: info@benthamscience.net

Hanieh Nadi-Yazdi

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Seyed Hassanian

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

References

  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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1002/ibd.21348 PMID: 20848530

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers