STAVROS MANOLAGAS, MD
Osteopathic Medicine at Markham St, Little Rock, AR

6660468, Dec 9, 2003

Oct 7, 1999

09/413958

Stavros C. Manolagas - Little Rock AR
Robert L. Jilka - Little Rock AR
Robert S. Weinstein - Little Rock AR
Teresita Bellido - Little Rock AR

Board of Trustees of the University of Arkansas - Little Rock AR

C12Q 100

435 4, 435 71

The present invention demonstrates that glucocorticoid-induced bone disease is due to changes in the birth and death rate of bone cells using a murine model of glucocorticoid excess as well as bone biopsy specimens obtained from patients with glucocorticoid-induced osteoporosis. This invention demonstrates that glucocorticoid administration increases apoptosis of mature osteoblasts and osteocytes and decreases bone formation rate and bone mineral density accompanied by defective osteoblastogenesis and osteoclastogenesis in the bone marrow.

6416737, Jul 9, 2002

Nov 19, 1999

09/443841

Stavros C. Manolagas - Little Rock AR
Teresita Bellido - Little Rock AR

Board of Trustees of the University of Arkansas - Little Rock AK

A61K 4900

424 92, 424 96, 436103, 436104, 436106, 436111, 436127, 514 75, 514102, 514114, 514141

The present invention is a method and composition to increase bone strength in a manner that decreases fracture incidence, which may or may not include increasing bone mineral density (“BMD”). The invention includes administering an effective amount of a bisphosphonate to a host in need thereof to increase bone strength, which inhibits the apoptosis of osteoblasts and osteocytes, without a significant effect on osteoclasts. In one embodiment, the bisphosphonate is not 1-amino-3-(N,N-dimethylamino)-propyliden-1,1-bisphosphonic acid or its pharmaceutically acceptable salt. An increase in osteoblast life span can lead to an increase in bone mass, i. e. , an anabolic effect. Preservation of osteocyte life span can increase bone strength, which may be disproportional to the increase in bone mass.

2002013, Sep 26, 2002

Jun 13, 2001

09/880710

Stavroula Kousteni - Little Rock AR, US
Stavros Manolagas - Little Rock AR, US

C12N015/85, C07K014/72

435/455000, 530/350000

This invention concerns the fundamental discovery of the understanding of the mechanism of action of steroidal nongenotropic effects and their relation to steroidal genotropic effects. It has been discovered that (i) steroidal nongenotropic effects and genotropic effects can be mediated by the same steroid receptor; (ii) both effects are ligand-induced; (iii) the nongenotropic effect occurs due to a ligand-induced activation of the ligand binding domain, which can be fast and loose fitting; (iv) the genotropic effect occurs due to a ligand-induced activation of the DNA-binding domain of the steroid receptor, which is typically a result of a slower, stronger interaction; and (v) the nongenotropic effect of a ligand interaction can be dissociated from the genotropic effect of a ligand interaction, in such a manner to effect a selective response. This invention also describes, for the first time, that certain steroids are capable of inducing a nongenotropic effect via binding to an unrelated steroid receptor

2004024, Dec 9, 2004

Dec 8, 2003

10/730751

Stavros Manolagas - Little Rock AR, US
Robert Jilka - Little Rock AR, US
Robert Weinstein - Little Rock AR, US
Teresita Bellido - Little Rock AR, US

Board of Trustees of the University of Arkansas

C12Q001/00

435/004000

The present invention demonstrates that glucocorticoid-induced bone disease is due to changes in the birth and death rate of bone cells using a murine model of glucocorticoid excess as well as bone biopsy specimens obtained from patients with glucocorticoid-induced osteoporosis. This invention demonstrates that glucocorticoid administration increases apoptosis of mature osteoblasts and osteocytes and decreases bone formation rate and bone mineral density accompanied by defective osteoblastogenesis and osteoclastogenesis in the bone marrow.

2003011, Jun 26, 2003

Jun 7, 2002

10/165380

Stavros Manolagas - Little Rock AR, US
John Katzenellenbogen - Urbana IL, US

A61K031/56

514/178000, 514/182000

A variety of bone anabolic compounds are useful for maintaining and/or increasing bone mass, density, and/or strength in mammals. Preferred compounds enhance bone anabolic activity while minimizing or eliminating undesirable feminizing or masculinizing effects.

2006012, Jun 8, 2006

Sep 27, 2005

11/236042

Stavros Manolagas - Little Rock AR, US
Teresita Bellido - Little Rock AR, US

C12Q 1/68

435006000

The invention pertains to the elucidation of the pro-apoptotic effect of glucocorticoids on osteocytes. The present invention provides methods to screen compounds that retain the anti-inflammatory properties of glucocorticoids yet do not result in the detrimental effect of bone loss and compound identified by the methods.

2005002, Feb 3, 2005

Apr 21, 2004

10/829028

Stavros Manolagas - Little Rock AR, US
Robert Jilka - Little Rock AR, US
Robert Weinstein - Little Rock AR, US
Teresita Bellido - Little Rock AR, US
Donald Bodenner - Little Rock AR, US
Stavroula Kousteni - Little Rock AR, US

The Board of Trustees of the University of Arkansas - Little Rock AR

G01N033/53, G01N033/567, A61K031/56

435007200, 514169000

The invention as disclosed provides a method to increase bone mass without compromising bone strength or quality, through the administration to a host of a compound that binds to the estrogen or androgen receptor without causing hormonal transcriptional activation.