METHODS FOR PREVENTING OR TREATING OSTEOARTHRITIS

• US 20170266168A1
• Filed: 09/14/2015
• Published: 09/21/2017
• Est. Priority Date: 09/18/2014
• Status: Abandoned Application

• Current Assignee: Rush University Medical Center (Rush University)
• Original Assignee: Rush University Medical Center (Rush University)
• Inventors: Chan, Deva, Li, Jun, Plaas, Anna H.K., Predescu, Daniel, Sandy, John D.
• Application Number:
  US15/512,325
• Publication Number:
  US 20170266168A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis

Abstract

One aspect of the invention provides a method for treating or preventing the development of osteoarthritis by administering to a subject in need of such treatment a composition including a therapeutically effective amount of an anti-fibrotic agent. In various embodiments, the anti-fibrotic agent is 5-methyl-1-phenylpyridin-2-one, tranilast, gamma-glutamyl transpeptidase inhibitor, fasudil, CC-930, T-5524, rosiglitazone, tocilizumab, E5564, TAK-242, GKT136901 or bosentan.

Claims

1. A method for treating or preventing the development of osteoarthritis, the method comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of an anti-fibrotic agent.

2. The method of claim 1, wherein the anti-fibrotic agent is selected from the group consisting of 5-methyl-1-phenylpyridin-2-one, tranilast, gamma-glutamyl transpeptidase inhibitor, fasudil, CC-930, T-5524, rosiglitazone, tocilizumab, E5564, TAK-242, GKT136901 and bosentan.

3. The method of claim 2, wherein the anti-fibrotic agent is 5-methyl-1-phenylpyridin-2-one.

4. The method of claim 1, wherein the composition further comprises at least one pharmaceutically acceptable carrier.

5. The method of claim 1, wherein the subject is a human subject.

6. The method of claim 1, wherein the anti-fibrotic agent at least partially normalizes the activation of at least one gene selected from the group consisting of Col1a1, Col1a2, Col2a1, Col3a1, Acan, Vcan, Has1, Has2, Has3, Itih2, and Tnfaip6.

7. The method of claim 6, wherein the anti-fibrotic agent at least partially normalizes the activation of at least two genes selected from the group consisting of Col1a1, Col1a2, Col2a1, Col3a1, Acan, Vcan, Has1, Has2, Has3, Itih2, and Tnfaip6.

8. The method of claim 1, wherein the anti-fibrotic agent at least partially normalizes the activation of at least one gene selected from the group consisting of the NF-κ

b pathway genes shown in FIG. 5A.

9. The method of claim 1, wherein the anti-fibrotic agent at least partially normalizes the activation of at least one gene selected from the group consisting of the fibrosis pathway genes shown in FIG. 5B.

10. The method of claim 1, wherein the composition is administered orally.

11. The method of claim 1, wherein the composition is administered by a route selected from the group consisting of the subcutaneous, intra-articular, intradermal, intravenous, intraperitoneal and intramuscular routes.

12. The method of claim 1, wherein the subject is a human subject having an injury to a joint selected from the group consisting of the knee, shoulder, hip, elbow, temporomandibular or ankle joints, or a joint of the hand, foot and spine.

13. The method of claim 1, wherein the subject is a human subject having a traumatic injury.

14. A method for treating an injury to a joint of a human or veterinary subject, comprising:

determining mRNA expression levels of a plurality of genes expressed in a tissue sample taken from an intra-articular region of the joint, the plurality of genes comprising at least the genes listed in FIG. 4;

calculating a reparative index score based on the mRNA expression levels of the plurality of genes, wherein the reparative index score is indicative of the quality of the repair response, and

administrating a the anti-fibrotic agent is selected from the group consisting of 5-methyl-1-phenylpyridin-2-one, tranilast, gamma-glutamyl transpeptidase inhibitor, fasudil, CC-930, T-5524, rosiglitazone, tocilizumab, E5564, TAK-242, GKT136901 and bosentan, wherein the anti-fibrotic agent is administrated depending on the reparative index score.

15. The method of claim 14, wherein the anti-fibrotic agent is 5-methyl-1-phenylpyridin-2-one.

16. The method of claim 14, wherein the tissue sample comprises material selected from the group consisting of synovial fluid, blood, cartilage, synovium, meniscal tissue, joint capsule lining, ligaments and combinations of at least two of these materials.

17. The method of claim 14, wherein calculating the reparative index score comprises:

comparing the mRNA expression levels with first standard expression levels of the plurality of genes and second standard expression levels of the plurality of genes, wherein the first standard expression levels are indicative of a reparative profile and wherein the second standard expression levels are indicative of a non-reparative profile; and

determining the reparative index score based on relative values of the mRNA expression levels, the first standard expression levels and the second standard expression levels.