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Antagonists of the Hedgehog Pathway as Therapeutics for the Treatment of Heterotopic Ossification, Vascular Calcification, and P

Posted Feb 12 2012 7:00pm

Description of Invention:
Heterotopic ossification (HO) results from osteoid formation of mature lamellar bone in soft tissue sites outside the skeletal periosteum (skeletal system), most commonly around proximal limb joints. HO can also be caused by genetic diseases such as progressive osseous heteroplasia (POH) and fibrodysplasia ossificans progressiva (FOP). Currently, all forms of HO lack adequate treatments and definite cure. Vascular calcification is a complex process that involves biomineralization and resembles osteogenesis. It is exacerbated during such conditions as diabetes, osteoporosis, menopause, hypertension, metabolic syndrome, chronic kidney disease, and end stage renal disease. In the present technology, the inventors describe novel methods for preventing or treating HO and vascular calcification using one or more antagonists of the Hedgehog pathway. The inventors, using both in vitro (limb culture experiments) and in vivo studies using Prx1-cre; Gsf/f mice model discovered that the antagonists of the Hedgehog pathway prevent formation of HO. The inventors also observed that Prx1-cre; Gsf/f mice developed calcification or mineralization around their blood vessels, and treatment with Hedgehog antagonists reduced mineralization throughout the body of these mice, including regions around the blood vessels, as observed by mineral staining. The antagonists that can be used to develop effective therapeutics include zerumbone epoxide, arcyriaflavin C, 5,6-dihyroxyarcyriaflavin A, physalin F, physalin B, arsenic trioxide (ATO), sodium arsenite, etc.

Applications:
Development of therapeutics for heterotopic ossification, vascular calcification, and pathologic mineralization.

Advantages:
Several clinically tested and FDA-approved Hedgehog antagonists are currently available and these compounds will expedite the commercial development of this technology.

Development Status:
  • Early-stage
  • Pre-clinical
  • In vitro data available
  • In vivo data available (animal)


Inventors:
Yingzi Yang (NHGRI)
Jean B Regard (NHGRI)


Patent Status:
HHS, Reference No. E-116-2011/0
US, Application No. 61/504,041 filed 01 Jul 2011


Collaborative Research Opportunity:
The National Human Genome Research Institute (NHGRI) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize antagonists of the Hedgehog pathway for treatment of ossification and calcification disorders. For collaboration opportunities, please contact Claire T. Driscoll at 301-594-2235 or cdriscoll@mail.nih.gov .


For Licensing Information Please Contact:
Suryanarayana Vepa Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: vepas@mail.nih.gov
Phone: 301-435-5020
Fax: 301-402-0220


Ref No: 2367

Updated: 02/2012

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