Lay Summary

Proposal No. IBD-0206
Principal Investigator:  Jon Lundberg, M.D., Ph.D.
Applicant Organization:  Karolinska Institutet (Stockholm, Sweden)
Project Title:  Nitrated fatty acids and inflammatory bowel disease
Period of Award:  March 1, 2008 – February 28, 2009

Preliminary studies indicate that nitroalkenes (or nitrated fatty acids) can be formed in the body and these compounds seem to have strong anti-inflammatory activity, mainly via stimulation of peroxisome proliferator-activated receptor gamma (PPAR-γ). Activation of PPAR- γ leads to a strong down-regulation of the host inflammatory response. The expression of PPAR-γ is particularly high in colon epithelial cells and these cells are therefore good candidate targets for compounds that act via this pathway. We will first test the anti-inflammatory effects of nitrated fatty acids in an animal model of IBD. If this is successful we hope to be able to move into clinical trials in IBD patients in the near future. By targeting one critical part of the inflammatory pathway instead of the entire cascade, we hope to be able to develop new drugs with fewer side effects than many of the drugs used today.