Targeted therapies for inflammatory bowel disease

摘要: Medical treatment of inflammatory bowel disease (IBD) has traditionally consisted administration anti-inflammatory drugs such as sulfasalazine, mesalazine, glucocorticosteroids, and more recently immunomodulating including azathioprine, methotrexate, cyclosporine. None these been primarily designed for use in IBD, most the precise mechanisms action are unknown. The development IBD long hindered by lack suitable animal models knowledge regulation (immunemediated) mucosal inflammation. In past decade cells involved inflammation, many proteins that lymphocytes, monocytes antigen-presenting to communicate, have characterized. Mice either or over-express often develop this not only greatly improved basic knowledge, but also provided elegant testing therapeutic interventions. Concurrently, rapid biotechnology resulted new classes now commonly known 'biologicals'. term 'biologicals' originally referred a group therapeutically administered endogenous antibodies, cytokines, naturally occurring cytokine-neutralizing proteins. However, biologicals extensively modified increase effects half-life, compounds antisense oligonucleotides, do occur naturally, usually categorized biologicals. Hence, better operational definition biological therapies is approaches all peptides, nucleic acids order specifically target cell activation, consequences thereof. Biological differ from traditional small molecules several aspects. Because interfere with single target, clinical efficacy interventions directly reflects pathogenic importance targets. As result class agents contributed current understanding pathogenesis IBD. Current allows (antibodies, oligonucleotides) intervention studies, thereby decreasing drug time. Most highly speciesspecific because extensive feasible, path bench bedside becomes even shorter. A second line targeted rapidly increased pathways through which receptors on membrane transmit signals nucleus, resulting transcriptional activation specific genes (the signal transduction pathways). Specific inhibitors components generated, some properties preclinical models. Finally, gene therapy aUows very manipulation function, although no trials initiated initiated. chapter fundamentals discussed. Although become test bed chronic diseases, number overwhelming, it should be noted one (treatment TNF-aneutralizing antibodies) at present approved Crohn's (CD).