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, diabetes, and many more significant diseases.

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 both mice and pigs that by targeting thrombospondin-1 and/or CD47, blood flow can be dramatically increased to ischemic tissues.  The same therapeutics also were found to protect tissues from ischemia/reperfusion injury.

Available for licensing and commercial development are:

• Compositions and methods of treating tissue ischemia and/or tissue damage due to ischemia, increasing blood vessel diameter, blood flow and tissue perfusion in the presence of vascular disease including peripheral vascular disease, atherosclerotic vascular disease and stroke.
• Compositions and methods for decreasing blood flow as in the case of cancer through mimicking the effects of thrombospondin-1 and CD47 on blood vessel diameter and blood flow.

Applications:

• Potential therapeutics for precise regulation of blood flow to tissues and organs.
• Efficient methods to increase tissue survival under conditions of trauma and surgery.
• Efficient methods for the treatment of elderly subjects using agents that affect thrombospondin-1 and CD47 and thereby affect tissue perfusion.
• Methods for treatment of ischemia/reperfusion injury as associated with transplant surgery

Market:

• People with ischemic disease are at increased risk of heart attack (myocardial infarction), stroke and peripheral vascular disease (PVD).  Ischemic heart disease attributes to more deaths, with 24 percent in the U.S., than any other cause.
• Cerebral ischemia is the third leading cause of death after heart diseases and cancer.
• Decreased blood flow underlies a significant number of chronic diseases that account for the majority of morbidity and mortality for elderly adults in this country.
• Cancer patients and traumatic injury victims requiring reconstructive surgery
• Burn patients requiring skin transplants
• Organ transplant patients

Development Status:

Early-stage of development (in vivo data available in mice and pigs)

PCT Application No. PCT/US2007/080647 filed 5 Oct 2007, which published as WO 2008/060785 on 22 May 2008 (HHS Reference No. E-227-2006/5-PCT-01)

Inventors:

Jeff S. Isenberg et al. (NCI)

Licensees Sought:

Available for licensing.

Collaborative Research Opportunity:

The National Cancer Institute Center for Cancer Research, Laboratory of Pathology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutics targeting CD47 or thrombospondin-1.  Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.