Recent insights into the molecular pathogenesis of Crohn s disease: a review of
emerging therapeutic targets
#MMPMID27042137
Manuc TE
; Manuc MM
; Diculescu MM
Clin Exp Gastroenterol
2016[]; 9
(?): 59-70
PMID27042137
show ga
Chronic inflammatory bowel diseases (IBDs) are a subject of great interest in
gastroenterology, due to a pathological mechanism that is difficult to explain
and an optimal therapeutic approach still undiscovered. Crohn's disease (CD) is
one of the main entities in IBD, characterized by clinical polymorphism and great
variability in the treatment response. Modern theories on the pathogenesis of CD
have proven that gut microbiome and environmental factors lead to an abnormal
immune response in a genetically predisposed patient. Genome-wide association
studies in patients with CD worldwide revealed several genetic mutations that
increase the risk of IBD and that predispose to a more severe course of disease.
Gut microbiota is considered a compulsory and an essential part in the
pathogenesis of CD. Intestinal dysmicrobism with excessive amounts of different
bacterial strains can be found in all patients with IBD. The discovery of
Escherichia coli entero-invasive on resection pieces in patients with CD now
increases the likelihood of antimicrobial or vaccine-type treatments. Recent
studies targeting intestinal immunology and its molecular activation pathways
provide new possibilities for therapeutics. In addition to antitumor necrosis
factor molecules, which were a breakthrough in IBD, improving mucosal healing and
resection-free survival rate, other classes of therapeutic agents come to focus.
Leukocyte adhesion inhibitors block the leukocyte homing mechanism and prevent
cellular immune response. In addition to anti-integrin antibodies, chemokine
receptor antagonists and SMAD7 antisense oligonucleotides have shown encouraging
results in clinical trials. Micro-RNAs have demonstrated their role as disease
biomarkers but it could also become useful for the treatment of IBD. Moreover,
cellular therapy is another therapeutic approach under development, aimed for
severe refractory CD. Other experimental treatments include intravenous
immunoglobulins, exclusive enteral nutrition, and granulocyte colony-stimulating
factors.
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