Method for treating adamts-5-associated disease

Details Method for treating adamts-5-associated disease Method for treating adamts-5-associated disease

A - Human Necessities

61

K

A61K 31/19 (2006.01) A61K 31/425 (2006.01) A61K 31/47 (2006.01) A61K 31/54 (2006.01) C12N 9/50 (2006.01) C12N 9/64 (2006.01)

Patent

CA 2547575

The present invention relates to methods of treating ADAMTS-S-associated diseases and particularly osteoarthritis comprising administering an agent capable an of modulating ADMATS-5 activity to a subject afflicted with the disease. The agent is preferably a biaryl sulfonamide compound. The invention is based, in part, on the discovery that transgenic animals that do not express functional ADAMTS-5 show a reduction in the degree of osteoarthritis after the induction of osteoarthritis as compared to WT animals. Furthermore, the ADAMTS-5 transgenic animals have reduced aggrecanase activity in articular tissue as compared to WT animals. These animals aye good models for ADAMTS-S- associated diseases, and for screening of drugs useful in the treatment and/or prevention of these diseases. These are no other animal models in which the deletion of the activity of a single gene is capable of abrogating the course of osteoarthritis. Accordingly, these animals also show that osteoarthritis can be prevented and/or treated by administering to a subject an ADAMTS-5 inhibitory agent and particularly an agent A0@0ble of inhibiting the aggrecanase activity of ADAMTS-5. Figure 1 illustrates the targeted disruption of the murine ADAMTS-5 gene.

La présente invention concerne un traitement des maladies associées à ADAMTS-5, et particulièrement l'ostéoarthrose, en administrant au sujet concerné un agent capable de moduler l'activité ADAMTS-5, en l'occurrence de préférence un composé à base de biaryl-sulfonamide. L'invention repose en partie sur la découverte que les animaux transgéniques qui n'expriment par d'ADAMT-S fonctionnel présentent un moindre degré d'atteinte après induction de l'ostéoarthrose que les sujets de type sauvage. Parallèlement, l'activité agrécanase des animaux transgéniques à ADAMTS-5 est également inférieure. Ces animaux sont de bons modèles pour les maladies associées à ADAMTS-5 ainsi que pour la recherche systématique de médicaments convenant au traitement et/ou à la prévention de ces maladies. Il n'y a aucun autre modèle animal dans lequel la suppression de l'activité d'un seul gène ne soit capable d'abroger le cours de l'ostéoarthrose. Il en résulte que ces animaux montrent également que l'ostéoarthrose peut se prévenir et/ou traiter par administration au sujet concerné d'un agent inhibiteur de l'ADAMTS-5, et plus particulièrement d'un agent capable d'inhiber l'activité agrécanase de l'ADAMTS-5.

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