Compositions and methods for treating articular cartilage disorders

US20060258588A1Inactive Publication Date: 2006-11-16NOVARTIS VACCINES & DIAGNOSTICS INC
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  • Compositions and methods for treating articular cartilage disorders

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example 1

Use of IGF-I in a Model of Canine Osteoarthritis

[0065] A canine study was conducted to evaluate the efficacy and safety of intra-articular administration of recombinant human insulin-like growth factor I (rhIGF-I) and a sustained-release formulation of rhIGF-I, referred to as Depo IGF-I, in a model of canine osteoarthritis (OA).

[0066] Fifty-six dogs underwent surgical transection of the right anterior cruciate ligament by the method of Pond and Nuki (Ann. Rheum. Dis. 32 (1973):887-888). Such transection induces joint instability, leading to production of erosions in the articular cartilage similar to those seen with human osteoarthritis. The animals were premedicated with atropine (0.02 mg / kg, intramuscular (IM)) and acetylpromazine (0.2 mg / kg, IM) prior to induction of anesthesia. Animals were anesthetized with methohexital (7-12 mg / kg, intravenous (IV)), then intubated and maintained in anesthesia with isoflurane inhalant anesthetic delivered through a volume-regulated respirato...

example 2

IGF-I Stimulation of Proteoglycan in Cell Culture

[0108] Chondrocytes were obtained from a human with osteoarthritis. Cells in suspension (alginate beads) were exposed to 100 ng / ml or 1,000 ng / ml rhIGF-I for 10 days. The IGF-I response (35S incorporation into proteoglycan) was assessed on days 3, 7, and 10. rhIGF-I was then removed from the media, and the IGF-I response was assessed again on days 14 and 21. Proteoglycan was measured in the media, the cell pellet, and in the alginate.

[0109] The subject's cells showed IGF-I stimulation of proteoglycan synthesis during the first 10 days as compared to the control cells, which were not exposed to rhIGF-I (FIG. 1). Further, chondrocytes continued to demonstrate enhanced proteoglycan synthesis from day 10 to day 14, four days after removal of IGF-I. These data provide additional evidence for the benefit of intermittent dosing in the treatment of osteoarthritis.

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Abstract

A method for treating mammalian articular cartilage disorders, more particularly osteoarthritis, and trauma-related cartilage injuries using insulin-like growth factor I (IGF-I) is provided. The method comprises increasing the amount of IGF-I at the diseased or injured articular site to a therapeutically effective level that is capable of maintenance and / or regeneration of cartilage, which is beneficial to the long-term treatment of osteoarthritis and trauma-related injuries to cartilage tissues. In one embodiment of the invention, single doses of at least 0.01 mg of pharmaceutically effective IGF-I are administered intermittently such that the duration of time off of therapy is greater than the time on therapy, more preferably with a frequency of administration of about once per week or less.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. application Ser. No. 10 / 199,449, filed Jul. 19, 2002; which is a continuation of U.S. application Ser. No. 09 / 285,554, filed Apr. 2, 1999; which claims the benefit of U.S. Provisional Application No. 60 / 080,683, filed Apr. 3, 1998, the contents of which are hereby incorporated herein in their entirety by reference.FIELD OF THE INVENTION [0002] This invention relates to methods for long-term treatment of mammalian articular cartilage disorders. These methods use therapeutic agents that preserve existing cartilage tissues or stimulate regeneration of cartilage to counteract the degenerative effects of the cartilage disorder or injury. BACKGROUND OF THE INVENTION [0003] Articular cartilage plays an essential role in the movement of mammalian joints. While synovial fluid within the joint cavity serves as a lubricant, the articular cartilage provides a superior smooth surface between adjacent bones,...

Claims

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Application Information

Patent Timeline
16 Nov 2006
Publication
US20060258588A1
IPC
A61K38/18; A61K38/30; A61K38/27; A61P19/00; A61P19/02; A61P43/00
CPC
A61K38/30; A61P19/00; A61P19/02; A61P43/00
Inventors
PIKE, MARILYN C.; WOLFGANG, GRUSHENKA H. I.