Methods of treating or preventing inflammation associated with an autoimmune disorder, particularly inflammatory bowel disease, via administration of muramyl peptide

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.

 

Applications:

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.

 

Development Status:

In vivo data are available in an experimental colitis mouse model, and in vitro data supporting mechanism of action also are available.

 

Relevant Publication:

T. Watanabe et al.  Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis.  J Clin Invest. 2008 Feb;118(2):545-559.  [PubMed abs]

 

 

 

PCT Application No. PCT/US2007/086117 filed 30 Nov 2007 (HHS Reference No. E-110-2006/0-PCT-02)

 

Inventors:
Warren Strober et al. (NIAID)

 

Licensing Status:
This technology is available for exclusive or non-exclusive licensing.

 

Collaborative Research Opportunity:
The NIAID Laboratory of Host Defenses, Mucosal Immunity Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology.  Please contact either Rosemary Walsh or Charles Rainwater at 301-496-2644 for more information.