Method for improving cartilage repair and/or preventing cartilage degeneration in a joint

Abstract

The invention is in the field of methods for medical treatment. It provides an improved method for repairing damaged cartilage and/or preventing cartilage degeneration in tissue, in particular in a joint by administering a pharmaceutically active agent directly into the fat pad of a joint. The pharmaceutically active agent is preferably selected from the group consisting of agents that stimulate chondrogenic differentiation and/or cartilage matrix synthesis; agents that inhibit osteogenesis and/or hypertrophy, anti-inflammatory agents, agents that inhibit apoptosis of chondrocytes, agents that inhibit senescence of chondrocytes and agents that enhance lubrication of a joint.

1 . Method for improving cartilage repair and/or the prevention of cartilage degeneration and/or managing joint related pain by administering a pharmaceutically active agent directly into the fat pad of a joint. 
     
     
         2 . Method according to  claim 1  wherein said pharmaceutically active agent is selected from the group consisting of agents that stimulate chondrogenic differentiation and/or cartilage matrix synthesis; agents that inhibit osteogenesis and/or hypertrophy, anti-inflammatory agents, agents that inhibit apoptosis of chondrocytes, agents that inhibit senescence of chondrocytes and agents that enhance lubrication of a joint. 
     
     
         3 . Method according to  claim 2  wherein said agents that stimulate chondrogenic differentiation and/or cartilage matrix synthesis are selected from the group consisting of TGF-β-1, 2, and 3, BMP-2-4-7, CDMP, GDF-5, IGF-1, FGF family, SMAD-1, -2, -3-4, -5, -6, -7, -8, EDF, PDGF, type II collagen, type IX collagen, cartilage-link protein, COMP and GlcAT-1, SOX5, SOX6, SOX9, MEF2C, Dlx5, Nkx2.5, PTHrP, Ihh, Wnt, CTGF. 
     
     
         4 . Method according to  claim 2  wherein said agents that inhibit osteogenesis and/or hypertrophy are selected from the group consisting of noggin, chordin, PTHrP, Ihh, Shh, DHH, Smad 6, 7, mIAP-1 and COX-1 and COX-2 inhibitors. 
     
     
         5 . Method according to  claim 2  wherein said anti-inflammatory agents are selected from the group consisting of II-1Ra, sIL-1R, ICE inhibitor, sTNFR, anti-TNF-antibodies, TACE inhibitor, TIMP-1,-2, MMP inhibitors, II-4, -10, -11, 13, GFAT, COX-1 and COX-2 inhibitors. 
     
     
         6 . Method according to  claim 2  wherein said agents that inhibit apoptosis of chondrocytes are selected from the group consisting of Bcl-2, Bcl-XL, anti-FasL, Akt, PI-3-kinase, NFkB and hyaluronan. 
     
     
         7 . Method according to  claim 2  wherein said agents that inhibit senescence of chondrocytes are selected from the group consisting of hTERT, NO (iNOS) antagonist and SOD. 
     
     
         8 . Method according to  claim 2  wherein said agents that enhance lubrication of a joint are selected from the group consisting of hyaluronan and superficial zone protein (SZP)/lubricin. 
     
     
         9 . Method according to  claim 1  wherein said pharmaceutically active agent is contained in a device suitable for controlled release of said agent. 
     
     
         10 . Method according to  claim 9  wherein said device is a biogel. 
     
     
         11 . Method according to  claim 10  wherein the biogel comprises a biocompatible polymer. 
     
     
         12 . Method according to  claim 10  wherein the biogel is biodegradable. 
     
     
         13 . Method according to  claim 10  wherein said biogel is selected from the group consisting of a hydrogel, a saccharide polymer, microspheres, liposomes, agarose, Carrageenans, Hyaluronan (Hyaff-11), PGA-scaffold, type II collagen-glycosaminoglycan scaffold, glycerol tripalmitate, OPF and gelatine microparticles, PEO-hydrogels with PLGA microspheres, OPF and gelatine microparticles, Collagen/chitosan/glycosaminoglycan with or without chitosan microspheres, P(NiPAAm-co-AAC)/HA hydrogels, collagens, PLA-PEG/IP-CHA and Gelatine/chondroitin/hyaluronate with or without gelatine microparticles