Title:
METHODS FOR INHIBITING MACROPHAGE COLONY STIMULATING FACTOR AND C-FMS-DEPENDENT CELL SIGNALING
Document Type and Number:
WIPO Patent Application WO2002087496
Kind Code:
A3
Abstract:
Described herein are methods of inhibiting M-CSF activity, and, in particular, M-CSF/c-fms dependent cell signaling. In a first embodiment of the invention, one administraters to a mammal viral vectors that deliver genes expressing antisense c-fms RNA; in a second embodiment, one induces in vivo production of a high-affinity soluble c-fms protein that competes for non-bound M-CSF; in a third embodiment, one administers a ribozyme-viral vector against c-fms mRNA; and in a fourth embodiment, one administers oligodeoxynucleotides that inhibit expression of c-fms gene product. The methods may be used to treat any disease in which M-CSF activity plays a role, and are particularly effective in treating and preventing atherosclerosis. Embodiments of the present invention are directed primarly, but not exclusively, to a method for treating and preventing cardiovascular disease by inhibiting receptors to M-CSF. Other embodiments of the present invention include any and all biologic and/or pathobiologic phenomena mediated in whole or in part by M-CSF singaling through its receptor. Pathobiologic phenomena inlcude, but are not limited to, disease entities such as osteoprosis, Alzheimer's disease, diabetes mellitus (Type 1 and/or Type 2), infectious disease, cancer, and inherited disorders characterized by defects in one or more components in the M-CSF signaling pathway.
Inventors:
RAJAVASHISTH TRIPATHI
Application Number:
PCT/US2002/012251
Publication Date:
March 27, 2003
Filing Date:
April 17, 2002
Export Citation:
Assignee:
CEDARS SINAI MEDICAL CENTER (US)
International Classes:
A61K38/17; A61K48/00; A61P7/12; A61P9/10; A61P19/10; A61P25/28; A61P35/00; C12N15/113; C12N15/27; C12N15/861; A61K38/00; (IPC1-7): A61K48/00; C07H21/02; C07H21/04; C12N15/85; C12N15/86; C12Q1/68
Other References:
BORYCKI ET AL.: "Repression of the CSF-1 receptor (c-fms proto-oncogene product) by antisense transfection induces G1-growth arrest in L6alpha1 rat myoblasts", ONCOGENE, vol. 10, no. 9, 4 May 1995 (1995-05-04), pages 1799 - 1811, XP002957651
HIMES ET AL.: "A highly conserved c-fms gene intronic element controls macrophage-specific and regulated expression", JOURNAL OF LEUKOCYTE BIOLOGY, vol. 70, no. 5, November 2001 (2001-11-01), pages 812 - 820, XP002957650
BORYCKI ET AL.: "Colony-stimulating factor 1 (CSF-1) is involved in an autocrine growth control of rat myogenic cells", EXPERIMENTAL CELL RESEARCH, vol. 218, no. 1, May 1995 (1995-05-01), pages 213 - 222, XP002957649
INABA ET AL.: "Transcription factor PU.1 mediates induction of c-fms in vascular smooth cells: a mechanism for phenotypic change to phagocytic cells", MOLECULAR AND CELLULAR BIOLOGY, vol. 16, no. 5, May 1996 (1996-05-01), pages 2264 - 2273, XP002957652
WU ET AL.: "The role of the c-fms oncogene in the regulation of HL-60 cell differentiation", ONCOGENE, vol. 5, no. 6, June 1990 (1990-06-01), pages 873 - 877, XP002957653
INABA ET AL.: "Involvement of transcription factor PU.1 in phenotypic transformation of vascular smooth muscle cells to macrophage-like cells", DOMYAKU KOKA, vol. 24, no. 4/5, January 1996 (1996-01-01), pages 187 - 192, XP002958544
BIRCHENALL-ROBERTS ET AL.: "Inhibition of murine monocyte proliferation by a colonystimulating factor-1 antisense oligodeoxynucleotide", THE JOURNAL OF IMMUNOLOGY, vol. 145, no. 10, 15 November 1990 (1990-11-15), pages 3290 - 3296, XP002957654
SANSILVESTRI ET AL.: "Early CD34 high cells can be separated into KIThigh cells in which transforming growth factor-beta (TGF-beta) downmodulates c-kit and KIT low cells in which anti-TGF-beta upmodulates c-kit", BLOOD, vol. 86, no. 5, 1 September 1995 (1995-09-01), pages 1729 - 1735, XP000569752
YOKOYAMA ET AL.: "Modulation of c-fms proto-oncogene in an ovarian carcinoma cell line by a hammerhead ribozyme", BRITISH JOURNAL OF CANCER, vol. 76, no. 8, March 1997 (1997-03-01), pages 977 - 982, XP002957655
HIMES ET AL.: "A highly conserved c-fms gene intronic element controls macrophage-specific and regulated expression", JOURNAL OF LEUKOCYTE BIOLOGY, vol. 70, no. 5, November 2001 (2001-11-01), pages 812 - 820, XP002957650
BORYCKI ET AL.: "Colony-stimulating factor 1 (CSF-1) is involved in an autocrine growth control of rat myogenic cells", EXPERIMENTAL CELL RESEARCH, vol. 218, no. 1, May 1995 (1995-05-01), pages 213 - 222, XP002957649
INABA ET AL.: "Transcription factor PU.1 mediates induction of c-fms in vascular smooth cells: a mechanism for phenotypic change to phagocytic cells", MOLECULAR AND CELLULAR BIOLOGY, vol. 16, no. 5, May 1996 (1996-05-01), pages 2264 - 2273, XP002957652
WU ET AL.: "The role of the c-fms oncogene in the regulation of HL-60 cell differentiation", ONCOGENE, vol. 5, no. 6, June 1990 (1990-06-01), pages 873 - 877, XP002957653
INABA ET AL.: "Involvement of transcription factor PU.1 in phenotypic transformation of vascular smooth muscle cells to macrophage-like cells", DOMYAKU KOKA, vol. 24, no. 4/5, January 1996 (1996-01-01), pages 187 - 192, XP002958544
BIRCHENALL-ROBERTS ET AL.: "Inhibition of murine monocyte proliferation by a colonystimulating factor-1 antisense oligodeoxynucleotide", THE JOURNAL OF IMMUNOLOGY, vol. 145, no. 10, 15 November 1990 (1990-11-15), pages 3290 - 3296, XP002957654
SANSILVESTRI ET AL.: "Early CD34 high cells can be separated into KIThigh cells in which transforming growth factor-beta (TGF-beta) downmodulates c-kit and KIT low cells in which anti-TGF-beta upmodulates c-kit", BLOOD, vol. 86, no. 5, 1 September 1995 (1995-09-01), pages 1729 - 1735, XP000569752
YOKOYAMA ET AL.: "Modulation of c-fms proto-oncogene in an ovarian carcinoma cell line by a hammerhead ribozyme", BRITISH JOURNAL OF CANCER, vol. 76, no. 8, March 1997 (1997-03-01), pages 977 - 982, XP002957655
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