Treatment of cartilage disorders

A barrier, cartilage technology, applied in the field of medicine, can solve problems such as ineffectiveness of damaged tissue

Active Publication Date: 2009-08-12
ARES TRADING SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Indeed current effective treatments for cartilage injuries focus on pain relief and are ineffective or barely effective in regeneration of damaged tissue

Method used

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  • Treatment of cartilage disorders
  • Treatment of cartilage disorders
  • Treatment of cartilage disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0190] Example 1: Disease Models and Long-Term Pharmacology in Animals

[0191] The significant in vivo therapeutic effect of FGF-18(170AA) using intra-articular (i.a.) administration was tested on different OA and damaged cartilage disease models. In different species (rats, dogs), the total therapeutically effective dose was demonstrated to be 3-40 μg / animal / week (i.a.). The results obtained from the above animal disease models (OA and cartilage defects) are summarized as follows:

[0192] Table 1: Summary information of pharmacology studies of FGF-18(170AA)

[0193]

[0194] Table 2: Summary information on pharmacology studies of FGF-18(170AA) (continued)

[0195]

[0196] a Discussed in detail below

Embodiment 11

[0197] Example 1.1: Rat meniscus tear OA model

[0198] method:

[0199] Male Lewis rats (5-10 / group) were operated to cause meniscus tear in the right knee joint. Doses of 0.3, 1, 3, or 10 μg (in saline) were administered by the i.a. route starting 19-21 days after surgery, and pharmacodynamic effects related to the dosing regimen were determined. These total doses were given as (i) a single dose, (ii) once weekly for 3 weeks (each injection being 1 / 3 of the total dose), or (iii) 3 weekly injections for 3 weeks (each injection being 1 / 3 of the total dose) for 3 weeks 1 / 9 of the total dose). At the end of treatment or 3 weeks after treatment, the right knee was collected for histopathological evaluation of potential effects. Injury assessment was performed in 3 distinct zones: 3 zones per section (1-lateral, 2-medial, 3-medial), taking into account regional differences across the medial tibial plateau. In surgical models of OA, the lateral (z1) and medial (z2) thirds are u...

Embodiment 12

[0223] Example 1.2: Dog Meniscotomy OA Model

[0224] Female beagles (3 / group) underwent unilateral mid-partial meniscotomy on the left knee one month before starting treatment, followed by saline or 3, 10 or 30 μg FGF-18 (170AA) once a week Beneficial effects on established OA were determined with treatment once or thrice weekly (1 / 3 divided doses) for three weeks.

[0225] After three weeks of treatment, the left knee was evaluated for signs of gross (3 / group) and microscopic (3 / group) meniscotomy-induced changes and synthetic responses. All but one dog had normal appetite and activity throughout the study. One dog in group 12 (YLI-8) died before the end of the study (day 17) due to aspiration pneumonia caused by repeated anesthesia for joint injections. All operated dogs in all groups developed typical degenerative changes on the medial tibia characterized by focal localized cartilage degenerative lesions. Femur injuries are rare. All dogs had thickening of the medial j...

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Abstract

This invention concerns the treatment of cartilage disorder and osteoarthritis in particular. More specifically, it relates to the use of FGF-18 in treatment regimens and for the manufacture of a medicament for the treatment of patients having a cartilage disorder such as osteoarthritis, such as for example knee osteoarthritis or secondary hip osteoarthritis. Specifically provided is a preferred treatment scheme comprising once weekly administration of an FGF-18 compound per treatment cycle.

Description

field of invention [0001] The invention belongs to the field of medicine, and relates to the treatment of cartilage disorders, in particular to the treatment of osteoarthritis. More specifically, it relates to the application of FGF-18 in the treatment regimen and the application in the preparation of medicines for the treatment of patients suffering from cartilage disorders such as osteoarthritis (such as knee arthritis or secondary hip arthritis), specifically provided are included in A preferred treatment regimen for weekly administration of FGF-18 in each treatment cycle. Background of the invention [0002] FGF-18 was identified as a member of the FGF family, which is most closely related to FGF8 and FGF17. Activities associated with FGF18 include stimulation of mesenchymal cell lines, particularly cardiomyocytes, osteoblasts and chondrocytes (US Patent No. 6,352,971). FGF18 binds and activates FGFR4 and the IIIc splice variants of FGFR3 and FGFR2. [0003] Bone remo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61P19/02
CPCA61K38/1825
Inventor A·吉莫C·H·雷德尔E·冯鲍尔
Owner ARES TRADING SA
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