In vivo data are available in an experimental colitis mouse model, and in vitro data supporting mechanism of action also are available.
The nucleotide-binding oligomerization domain 2 (NOD2) protein plays a key role in innate immunity as a sensor of muramyl dipeptide (MDP), a breakdown product of bacterial peptidoglycan. Bacterial peptidoglycan promotes the innate immune response through the activation of Toll-like receptor 2 (TLR2), which ultimately provokes inflammation. Activation of NOD2 by MDP negatively regulates the activity of TLR2, and thus reduces inflammation.
The inventors have demonstrated that administration of MDP prevents the development of experimental colitis in mice. They have also determined that MDP reduces pro-inflammatory cytokine production from multiple Toll-like receptors, and that this reduction arises from the induction of IFN regulatory factor 4 (IRF4). The technology includes methods of treating or preventing inflammation associated with an autoimmune disorder, particularly inflammatory bowel disease, via administration of muramyl peptide; also included are methods of reducing symptoms characteristic of inflammation via administration of muramyl peptide.
This technology has potential as an anti-inflammatory therapy for autoimmune or other inflammation-associated diseases, particularly inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.