INNATE IMMUNITY, C-REACTIVE PROTEIN AND WOUND HEALING

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The acute phase host defense response (APR) is a survival mechanism of innate (non-specific, natural) immunity, triggered by the body as an immediate response to any minor or major threat to tissue integrity. Any damage or breach of tissues, such as occurs in wounds, compromises two important functions of innate immunity, 1.) as a barrier to the entry and movement of substances, and 2.) as a matrix within which reactions of host defenses and tissue repair are signaled and coordinated. A key protein of the APR is C-reactive protein (GRP). Recently, a conformational analog of CRP (i.e. mCRP) has been studied as a self- polymerizing protein naturally found in healthy, fibrous connective tissues. Intravenous mCRP has therapeutic activity in various animal models of cancer and infectious disease. This study will examine the rate and extent of tissue regeneration and repair of both partial thickness and full thickness wounds topically treated with recombinant mCRP (rmCRP), in both normal and impaired wound healing models. The goal of this work is to establish the safety and effectiveness of introducing a protein of innate immunity and the APR into injured tissues, and to establish the commercial potential of rmCRP for wound healing indications. PROPOSED COMMERCIAL APPLICATIONS: The discovery of mCRP as a naturally-occurring analog of CRP may one day be considered a key bridge to exploiting the natural (innate) immune system to therapeutic advantage. By depositing in tissues, mCRP may be used as a primary therapy to increase barriers (against infections, metastases, and inflammation), and as an adjunctive therapy to amplify beneficial reactions of the acute phase response. Essentially all patients with weakened tissues could be targeted for treatment. Because mCRP is a component of the "primitive" host defense system, it may be particularly effective in immunosuppressed individuals with impaired healing mechanisms. A recombinant form of mCRP suitable for commercialization is already available in large quantities.