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Methods Of Preventing Tissue Ischemia

Background:
The National Cancer Institute's Laboratory of Pathology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutics targeting vasodialation.

Technology:
Nitric oxide (NO) plays an important role as a major intrinsic vasodilator, and increases blood flow to tissues and organs. Disruption of this process leads to peripheral vascular disease, ischemic heart disease, stroke, vascular insufficiency associated with diabetes, and many more diseases that are significant.

Researchers at the NIH have discovered that the matrix protein thrombospondin-1 blocks the beneficial effects of NO, and prevents it from dilating blood vessels and increasing blood flow to organs and tissues.  Additionally, the inventors discovered that this regulation requires interaction with thrombospondin-1's cell receptor CD47. Murine studies revealed that, in the presence of NO, genetically altered mice, lacking either thrombospondin-1 or CD47, showed dramatically improved blood flow and tissue oxygenation.  The inventors have also shown in mice, rats, and pigs that by targeting thrombospondin-1 and/or CD47, blood flow can be dramatically increased to ischemic tissues.  

This invention has numerous potential applications, including increasing tissue survival under conditions of trauma and surgery, including skin grafting, as well as potential therapeutics for vascular disease, ischemic heart disease, stroke, and diabetes.  In addition to increasing blood flow to tissues and organs, this technology can be used to decrease blood flow and may have potential applications in cancer treatment.

Further R&D Needed:

• Pharmacokinetic and dosing optimization of existing antisense therapeutics
• Humanization of antibody therapeutics
• Development and optimization of small molecule analogs with oral availability

• Ability to develop therapeutics for precise regulation of blood flow to tissues and organs
• Potential to treat tissue ischemia, tissue damage due to ischemia, stroke, heart disease, diabetes, cancer, and numerous other significant diseases
• Ability to develop efficient methods to increase tissue survival under conditions of trauma and surgery