STAMP, A Novel Cofactor and Possible Steroid Sparing Agent, Modulates Steroid-induced Induction or Repression of Steroid Recepto

Description of Invention:
Steroid hormones such as androgens, glucocorticoids, and estrogens are used in the treatments of many diseases. They act to regulate many physiological responses by binding to steroid receptors. However, because steroid receptors are expressed in many tissues, efforts to therapeutically modify the effects of steroid hormones on a specific tissue or on a specific receptor of the steroid receptor family often cause undesirable effects in other tissues or on other receptors. STAMP (SRC-1 and TIF-2 Associated Modulatory Protein), a novel protein that acts to lower the concentration of steroid hormone needed to induce (or repress) selected target genes by regulating steroid receptor synthesis, offers an novel approach for reducing the severity of unwanted side-effects, thereby increasing the ability to use steroid hormone therapies.

Applications:

• Diseases requiring chronic steroid treatment such as rheumatoid arthritis, psoriatic arthritis, asthma, inflammatory and auto-immune diseases;
• Diseases characterized by excess or deficiency of glucocorticoids such as obesity, diabetes, hypertension, Cushing’s Syndrome, Parkinson’s Disease, Addison’s Disease;
• Diseases in which glucocorticoid-responsive gene expression is deranged, so deranging carbohydrate, protein or lipid metabolism;
• Cancers responsive to androgen or estrogen, such as breast cancer or prostate cancer;
• Therapeutic applications related to male or female hormone replacement, symptoms related to menopause, birth control, menstrual cycle/amenorrhea, fertility or endometriosis.

Advantages:

• STAMP reduces the severity of unwanted side-effects of steroid hormone therapies;
• STAMP modulates the gene induction properties of androgen and progesterone receptors;
• STAMP modulates both induction and repression properties of glucocorticoid receptors;
• STAMP is inactive toward alpha and beta estrogen receptors, thyroid receptor beta, PPAR gamma 2, retinoid receptor alpha or RXR alpha;
• The siRNAs could be useful as therapeutics.

Development Status:

• STAMP, a protein which is a novel nuclear receptor cofactor, has been identified;
• STAMP siRNAs have been shown to change the dose response curve of endogenous glucocorticoid receptor induced genes;
• A STAMP antibody has been prepared.

Further Development Required:

• Further in-vivo studies into the role of STAMP in glucocorticoid receptor-mediated repression;
• Further study into the activity of STAMP in androgen receptor-mediated responses;
• Investigation into the mechanism of action of STAMP;
• Development of STAMP knockout mouse.

Inventors:
S. Stoney Simons (NIDDK)
Yuanzheng He (NIDDK)


Patent Status:
HHS, Reference No. E-056-2004/0
US, Application No. 11/510,859 filed 25 Aug 2006


Related Technologies:
PCT, Application No. PCT/US01/09395 filed 23 Mar 2001, Reference No. E-015-2000/0


Relevant Publication:

1. Y He and SS Simons Jr. STAMP: A Novel Predicted Factor Assisting TIF2 Actions in Glucocorticoid Receptor–mediated Induction and Repression. Mol Cell Biol. 2007 Feb;27(4);1467-1485. [ PubMed abs ]

Licensing Status:
Available for exclusive and non-exclusive licensing.

Collaborative Research Opportunity:
The National Institute of Diabetes, Digestive and Kidney Diseases, Laboratory of Molecular and Cellular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. Please contact Dr. Stoney Simons, Chief, Steroid Hormones Section (NIDDK), at steroids@helix.nih.gov ; Tel: 301-496-6796 for more information.


Portfolios:
Internal Medicine
Internal Medicine - Therapeutics
Rare Diseases



For Additional Information Please Contact:
Tara Kirby Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: tk200h@nih.gov
Phone: 301-435-4426
Fax: 301-402-0220


Ref No: 1033

Updated: 05/2007