Pan-selectin antagonism improves psoriasis manifestation in mice and man.

Abstract

The selectin family of vascular cell adhesion molecules is comprised of structurally related carbohydrate binding proteins, which mediate the initial rolling of leukocytes on the activated vascular endothelium. Because this process is one of the crucial events in initiating and maintaining inflammation, selectins are proposed to be an attractive target for the development of new antiinflammatory therapeutics. Here, we demonstrate that the synthetic pan-selectin antagonist bimosiamose is effective in pre-clinical models of psoriasis as well as in psoriatic patients. In vitro bimosiamose proved to be inhibitory to E- or P-selectin dependent lymphocyte adhesion under flow conditions. Using xenogeneic transplantation models, bimosiamose reduced disease severity as well as development of psoriatic plaques in symptomless psoriatic skin. The administration of bimosiamose in patients suffering from psoriasis resulted in a reduction of epidermal thickness and lymphocyte infiltration. The clinical improvement was statistically significant (P=0.02) as analyzed by comparison of psoriasis area and severity index before and after treatment. Assessment of safety parameters showed no abnormal findings. These data suggest that pan-selectin antagonism may be a promising strategy for the treatment of psoriasis and other inflammatory diseases.

• Authors: Markus Friedrich, Daniel Bock, Sandra Philipp, Nina Ludwig, Robert Sabat, Kerstin Wolk, Sabine Schroeter-Maas, Ewald Aydt, Sewon Kang, Tomas Norman Dam, Rainer Zahlten, Wolfram Sterry, Gerhard Wolff
• Journal: Archives of dermatological research (Arch Dermatol Res) Vol. 297 Issue 8 Pg. 345-51 (Feb 2006) ISSN: 0340-3696 [Print] Germany
• PMID: 16362415 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Hexanes
• P-Selectin
• bimosiamose
• Mannose

Topics

• Adult
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Cell Adhesion (drug effects)
• Cell Line
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Endothelium, Vascular (pathology, physiopathology)
• Epidermis (chemistry, pathology)
• Female
• HL-60 Cells
• Hexanes (blood, pharmacology, therapeutic use)
• Humans
• Jurkat Cells
• Leukocytes (pathology, physiology)
• Male
• Mannose (analogs & derivatives, blood, pharmacology, therapeutic use)
• Mice
• Mice, SCID
• Middle Aged
• P-Selectin (analysis, physiology)
• Pilot Projects
• Psoriasis (blood, drug therapy, pathology, physiopathology)
• T-Lymphocytes (pathology)