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
R&D Status: Pre-clinical, in
vivo data available in mice, rats, and pigs
IP Status: PCT Application No.
PCT/US2007/080647 filed 5 Oct 2007, which published as WO
2008/060785 on 22 May 2008
Value Proposition:
- 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
Contact Information:
John D. Hewes, Ph.D.
NCI Technology Transfer Center
Tel: 301-435-3121
Email: hewesj@mail.nih.gov
Please reference advertisement #726
Revised 12/8/2008