COMBINATION OF AN IMMUNOSUPPRESSANT AND A PPAR GAMMA AGONIST FOR THE TREATMENT OF AN UNDESIRABLE IMMUNE RESPONSE
A method for the treatment or prevention of an undesirable immune response, comprising the simultaneous administration of an immunosuppressant such as cyclosporine and a PPAR-gamma agonist, such as pioglitazone or rosiglitazone. Undesirable immune responses include, for example, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, or transplant rejection.
1 . A method for the treatment or prevention of an undesirable immune response, comprising the simultaneous administration of an immunosuppressant and a PPAR-gamma agonist.
2 . A method according to claim 1 , comprising:
(a) an initial treatment phase comprising the simultaneous administration of an immunosuppressant and a PPAR-gamma agonist;
(b) a subsequent treatment phase comprising the administration of a PPAR-gamma agonist without the immunosuppressant of phase (a).
3 . A method according to claim 1 , wherein, comprising:
(a) an initial treatment phase comprising the simultaneous administration of an immunosuppressant and a PPAR-gamma agonist;
(b) a subsequent treatment phase comprising the administration of a PPAR-gamma agonist without an immunosuppressant.
4 . A method according to claim 1 , wherein, the immunosuppressant is utilized at a level which is sub-therapeutic in the absence of the PPAR-gamma agonist.
5 . A method according to claim 1 , wherein, the PPAR-gamma agonist is farglitazar.
6 . A method according to claim 1 , wherein, the PPAR-gamma agonist is a thiazolidinedione.
7 . A method according to claim 6 , wherein the thiazolidinedione is pioglitazone or rosiglitazone.
8 . A method according to claim 7 , wherein the thiazolidinedione is rosiglitazone.
9 . A method according to claim 1 , wherein, the immunosuppressant is not a cyclosporin.
10 . A method according to claim 9 , wherein the immunosuppressant is not cyclosporin A.
11 . A method according to claim 1 , wherein, the immunosuppressant is a macrolide.
12 . A method according to claim 11 , wherein the immunosuppressant is selected from pimecrolimus, tacrolimus and sirolimus.
13 . A method according to claim 12 , wherein the immunosuppressant is tacrolimus.
14 . A method according to claim 1 , wherein the immunosuppressant is cyclosporin A.
15 . A method according to claim 1 , wherein, the immunosuppressant is a biological immunosuppressant.
16 . A method according to claim 1 , wherein, the immune response comprises chronic inflammation.
17 . A method according to claim 1 , wherein, the immune response comprises tissue remodeling.
18 . A method according to claim 17 , wherein the immune response comprises a cellular infiltration.
19 . A method according to claim 17 , wherein the immune response comprises vascular occlusion.
20 . A method according to claim 17 , wherein the immune response comprises fibrosis.
21 . A method according to claim 1 , wherein, the undesirable immune response is a transplant rejection
22 . A method according to claim 21 , wherein the transplant is a solid organ transplant.
23 . A method according to claim 22 , wherein the solid organ transplant is selected from the group consisting of: kidney, liver, heart, lung, small bowel and limb transplants.
24 . A method according to claim 21 , wherein the transplant is a bone marrow transplant.
25 . A method according to claim 21 , wherein the initial treatment phase (a) commences following transplantation.
26 . A method according to claim 25 , wherein the initial treatment phase (a) is preceded by a pre-treatment phase comprising the administration of a PPAR-gamma agonist without an immunosuppressant.
27 . A method according to claim 1 , wherein, the undesirable immune response is an autoimmune disorder.
28 . A method according to claim 27 , wherein the autoimmune disorder is selected from the group consisting of: rheumatoid arthritis, psoriasis and systemic lupus erythematosus.
29 . A method according to claim 28 , wherein the autoimmune disorder is psoriasis.
30 . A method according to claim 28 , wherein the autoimmune disorder is rheumatoid arthritis.
31 . A method according to claim 28 , wherein the autoimmune disorder is systemic lupus erythematosus.
32 . A method according to claim 27 , wherein the undesirable immune response is a disorder with an autoimmune component.
33 . A method according to claim 32 , wherein the disorder with an autoimmune component is selected from the group consisting of: inflammatory bowel disease (including ulcerative colitis and Crohn's disease), Hashimoto's thyroiditis, pernicious anemia, Addison's disease, type I diabetes, systemic dermatomyositis, Sjogren's syndrome, multiple sclerosis, myasthenia gravis, Reiter's syndrome and Grave's disease.
34 . A method according to claim 32 , wherein the disorder with an autoimmune component is inflammatory bowel disease.
35 . A method according to claim 32 , wherein the disorder with an autoimmune component is multiple sclerosis.
36 . A method according to claim 27 , wherein the undesirable immune response is a disorder with an inflammatory component and which may or may not be autoimmune related.
37 . A method according to claim 36 , wherein the disorder with an with an inflammatory component and which may or may not be autoimmune related is atherosclerosis.
38 . A pharmaceutical composition comprising an immunosuppressant and a PPAR-gamma agonist.
39 . A pharmaceutical composition according to claim 38 , additionally comprising a pharmaceutically acceptable diluent or carrier.
40 - 60 . (canceled)