Title:
METHODS AND COMPOSITIONS FOR MODULATING CILIARY NEUROTROPHIC FACTOR ACTIVITY
Document Type and Number:
WIPO Patent Application WO2000063357
Kind Code:
A3
Abstract:
Methods and compositions for altering, or modulating CNTF activity by altering or modulating cytokine inhibitor activity are provided. Specifically encompassed are methods and compositions to alter activity of cytokine inhibitors such as SOCS-1, -2, and -3. SOCS-3 expression is rapidly induced by CNTF treatment in regions of the hypothalmus that are known to be involved in the regulation of body weight. As described herein, a SOCS-3-mediated CNTF cell-signaling inhibitory pathway exists, suggesting that SOCS-3 is a negative regulator of CNTF signal-transduction in the brain. Since CNTF treatment of animals suppresses appetite and induces weight loss, inhibition of SOCS-3 expression or activity is a potential target for the development of drugs aimed at improving CNTF sensitivity or prolonging CNTF activity in a mammal and inducing weight loss. Thus, altering SOCS-3 activity provides a means for modulating CNTF-induced cell signaling and therefore modulating bodyweight.
Inventors:
FLIER JEFFREY S (US)
BJOERBAEK CHRISTIAN (US)
BJOERBAEK CHRISTIAN (US)
Application Number:
PCT/US2000/010693
Publication Date:
January 25, 2001
Filing Date:
April 20, 2000
Export Citation:
Assignee:
BETH ISRAEL HOSPITAL (US)
FLIER JEFFREY S (US)
BJOERBAEK CHRISTIAN (US)
FLIER JEFFREY S (US)
BJOERBAEK CHRISTIAN (US)
International Classes:
C07K14/575; G01N33/50; A61K38/00; (IPC1-7): A61K48/00; C12N5/10; C12N15/11; A61K31/7088; G01N33/50; A61K38/18; A61P25/00; A61P3/00
Domestic Patent References:
| WO1998022128A1 | 1998-05-28 | |||
| WO1998020023A1 | 1998-05-14 | |||
| WO1999040946A2 | 1999-08-19 |
Other References:
BJORBAEK C ET AL: "Identification of SOCS -3 as a potential mediator of central leptin resistance.", MOLECULAR CELL, (1998 MAR) 1 (4) 619-25., XP002099320
DATABASE INTERNET 23 March 1998 (1998-03-23), "Discovery in molecule that inhibits the anti-obesity horhome, leptin may curb obesity", XP002152970
DATABASE INTERNET 21 May 1998 (1998-05-21), CROMIE WJ: "Knocking the SOCS off obesity", XP002152971
ECONOMIDES, ARIS N. ET AL: "Designer cytokines: targeting actions to cells of choice", SCIENCE (WASHINGTON, D. C.) (1995), 270(5240), 1351-3, XP002072653
WEIS J ET AL: "Increased expression of CNTF receptor alpha in denervated human skeletal muscle.", JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, (1998 SEP) 57 (9) 850-7., XP000960714
BJORBAEK CHRISTIAN ET AL: "Activation of SOCS-3 messenger ribonucleic acid in the hypothalamus by ciliary neurotrophic factor.", ENDOCRINOLOGY, vol. 140, no. 5, May 1999 (1999-05-01), pages 2035 - 2043, XP000960671, ISSN: 0013-7227
DATABASE INTERNET 23 March 1998 (1998-03-23), "Discovery in molecule that inhibits the anti-obesity horhome, leptin may curb obesity", XP002152970
DATABASE INTERNET 21 May 1998 (1998-05-21), CROMIE WJ: "Knocking the SOCS off obesity", XP002152971
ECONOMIDES, ARIS N. ET AL: "Designer cytokines: targeting actions to cells of choice", SCIENCE (WASHINGTON, D. C.) (1995), 270(5240), 1351-3, XP002072653
WEIS J ET AL: "Increased expression of CNTF receptor alpha in denervated human skeletal muscle.", JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, (1998 SEP) 57 (9) 850-7., XP000960714
BJORBAEK CHRISTIAN ET AL: "Activation of SOCS-3 messenger ribonucleic acid in the hypothalamus by ciliary neurotrophic factor.", ENDOCRINOLOGY, vol. 140, no. 5, May 1999 (1999-05-01), pages 2035 - 2043, XP000960671, ISSN: 0013-7227
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