The main functions of the Gastrointestinal (GI) tract are digestion and absorption of nutrients from ingested food and excretion of waste products. The GI tract promotes breakdown of complex, insoluble food substances to simpler molecules that facilitates absorption. The gastric mucosa plays a vital role in maintaining the mucosal integrity to protect the stomach from continuous exposure to noxious substances.
Inflammatory bowel diseases mainly occur due to prolonged inflammation of the gastrointestinal (GI) tract as a result of abnormal immune responses, though the clear-cut aetiology of these conditions remains unspecific. Most commonly observed conditions under this group are Crohn’s disease (CD) and Ulcerative colitis (UC). Crohn’s disease may affect any part of the GI tract, while Ulcerative colitis, as the name suggests, particularly affects the colon alone.
Inflammatory Bowel Diseases (IBD) currently affect approximately 0.5% of the Western world’s population. Researchers have identified a recent steady increase in the occurrence of CD and UC in populations of both developed and developing countries. The globally occurring cases increased from 3.7 million to over 6.8 million between the years 1990 to 2017.
Composition and mechanism of action
Issar has developed a novel non-biologic, non-steroidal, synthetic small peptide of 10 amino acids, for angiogenesis related diseases and inflammatory disorders. This novel peptide drug designated as IS 217 targets the VEGFR-2 which is the major receptor for angiogenesis function. Issar’s IS-217, has successfully proven its potential to arrest angiogenesis and reduce inflammatory cytokine levels in preclinical studies.
Preclinical trials
The in-vivo study using imiquimod animal model via subcutaneous administration showed IS-217 alone as a highly effective agent. The effects are either comparable or even better than the positive control group which was administrated with Betamethasone & Methotrexate.
Results
These results demonstrate that IS-217 targets VEGFR-2 by downregulating p38 kinases and proinflammatory IL-23 and IL-17 secretion. Considering these factors together; our study provides evidence of IS-217’s potential to treat inflammatory conditions such as Psoriasis and IBD by subcutaneous administration of an antiangiogenic compound.