COMPOSITIONS AND METHODS FOR MODULATING BONE MINERAL DEPOSITION

Title:

COMPOSITIONS AND METHODS FOR MODULATING BONE MINERAL DEPOSITION

Document Type and Number:

WIPO Patent Application WO2002092020

Kind Code:

A3

Abstract:

The key function ot TNAP in bone is degradation of PPi to remove this mineralization inhibitor and provide free phosphate for apatite deposition. PC-1 is a direct antagonist of TNAP function. ANK antagonizes TNAP-dependent matrix calcification. Specifically, the activity of PC-1 inhibits initial MV apatite deposition, but ANK inhibits propagation of apatite outside the MVs. Furthermore, loss of function of the two distinct skeletal TNAP antagonists, PC-1 and ANK, ameliorates TNAP deficiency-associated osteomalacia in vivo. Conversely, the hyperossification associated with both PC-1 null mice and ANK-deficient (ank/ank) mice is ameliorated by deficiency of TNAP in vivo.

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Inventors:

MILLAN JOSE LUIS (US)
TERKELTAUB ROBERT (US)

Application Number:

PCT/US2002/009021

Publication Date:

March 18, 2004

Filing Date:

March 22, 2002

Export Citation:

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Assignee:

BURNHAM INST (US)
MILLAN JOSE LUIS (US)
TERKELTAUB ROBERT (US)

International Classes:

A61K31/00; C07K14/705; C07K16/40; C12N9/16; C12N15/85; G01N33/50; G01N33/68; A61K38/00; (IPC1-7): A01N61/00; A01N37/18; A61K31/00; A61K38/00; A61K38/28; C07H21/02; C07H21/04; C07K16/00; C12P19/34; C12Q1/68

Foreign References:

US5773226A

1998-06-30

Other References:

LOTZ M. ET AL.: "Interleukin 1-beta suppresses transforming growth factor-induced inorganic pyrophosphate (PPi) production and expression of the PPi-generating enzyme PC-1 in human chondrocytes", PROC. NATL. ACAD. SCI. USA, vol. 92, October 1995 (1995-10-01), pages 10364 - 10368, XP002965036
DATABASE PROQUEST [online] BEERSTEN ET AL.: "Root development in mice lacking functional tissue non-apecific a lkaline phosphatase gene: inhibition of acellular cementum formation", XP002965037

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