Methods for the treatment of immune disorders

Patent metadata

Field	Value
Publication number	US-9439884-B2
Application number	US-201214122611-A
Country	US
Kind code	B2
Filing date	May 29, 2012
Priority date	May 26, 2011
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

Abstract

The invention features methods of treating an immune disorder characterized by elevated Pin1 marker levels in a subject by administering a retinoic acid compound. Additionally, the invention features methods of treating immune disorders (e.g., immune disorders characterized by elevated Pin1 marker levels) by administering a retinoic acid compound in combination with an anti-inflammatory, anti-viral, or anti-microbial compound.

First claim

What is claimed is:

1. A method of reducing elevated Pin1 activity in a subject having elevated levels of a Pin1 marker, comprising the step of administering to said subject a therapeutically effective amount of a retinoic acid compound, wherein said subject suffers from an immune disorder characterized by dysregulation of Toll-like receptor and/or type 1 interferon, and wherein said subject has elevated levels of a Pin1 marker.

2. A method of reducing elevated Pin1 activity in a subject, comprising the steps of determining Pin1 activity levels in a sample from said subject; and administering a therapeutically effective amount of a retinoic acid compound to said subject if said sample from said subject is determined to have elevated Pin1 activity levels, wherein said subject suffers from an immune disorder characterized by dysregulation of Toll-like receptor and/or type 1 interferon.

3. The method of claim 1 , further comprising the administration of a second therapeutic compound, wherein said second therapeutic compound is an anti-inflammatory compound, anti-microbial compound, or anti-viral compound.

4. The method of claim 1 , wherein said Pin1 activity is reduced by Ser71 phosphorylation of Pin1.

5. The method of claim 1 , further comprising determining Pin1 activity levels in said sample after said administration of a retinoic acid compound.

6. The method of claim 1 , wherein said retinoic acid compound is selected from the group consisting of 13-cis-retinoic acid and all-trans-retinoic acid.

7. The method of claim 1 , wherein said retinoic acid compound is selected from the group consisting of retinol, retinyl acetate, retinal, and AC-55649.

8. The method of claim 1 , wherein said sample is selected from the group consisting of blood, urine, tissue biopsies, lymph, saliva, phlegm, and pus.

9. The method of claim 1 , wherein said elevated Pin1 activity level is due to an inherited trait or a somatic mutation.

10. The method of claim 3 , wherein said second therapeutic compound is selected from the group consisting of corticosteroids, NSAIDs, COX-2 inhibitors, biologics, small molecule immunomodulators, non-steroidal immunophilin-dependent immunosuppressants, 5-amino salicylic acid, DMARDs, hydroxychloroquine sulfate, and penicillamine.

11. The method of claim 3 , wherein said second therapeutic compound is selected from the group consisting of microtubule inhibitors, topoisomerase inhibitors, platins, alkylating agents, and anti-metabolites.

12. The method of claim 3 , wherein said second therapeutic compound is selected from the group consisting of 1-D-ribofuranosyl-1,2,4-triazole-3 carboxamide, 9→2-hydroxy-ethoxy methylguanine, adamantanamine, 5-iodo-2′-deoxyuridine, trifluorothymidine, interferon, adenine arabinoside, protease inhibitors, thymidine kinase inhibitors, sugar or glycoprotein synthesis inhibitors, structural protein synthesis inhibitors, attachment and adsorption inhibitors, and nucleoside analogues such as acyclovir, penciclovir, valacyclovir, and ganciclovir.

13. The method of claim 3 , wherein said second therapeutic compound is administered at a low dosage.

14. The method of claim 3 , wherein said retinoic acid compound and said second therapeutic compound are formulated together.

15. The method of claim 1 , wherein said immune disorder is related to increased susceptibility to infection.

16. The method of claim 1 , wherein said immune disorder is selected from the group consisting of acne vulgaris; acute respiratory distress syndrome; Addison's disease; adrenocortical insufficiency; adrenogenital ayndrome; allergic conjunctivitis; allergic rhinitis; allergic intraocular inflammatory diseases, ANCA-associated small-vessel vasculitis; angioedema; ankylosing spondylitis; aphthous stomatitis; arthritis, asthma; atherosclerosis; atopic dermatitis; autoimmune disease; autoimmune hemolytic anemia; autoimmune hepatitis; Behcet's disease; Bell's palsy; berylliosis; bronchial asthma; bullous herpetiformis dermatitis; bullous pemphigoid; carditis; celiac disease; cerebral ischaemia; chronic obstructive pulmonary disease; cirrhosis; Cogan's syndrome; contact dermatitis; COPD; Crohn's disease; Cushing's syndrome; dermatomyositis; diabetes mellitus; discoid lupus erythematosus; eosinophilic fasciitis; epicondylitis; erythema nodosum; exfoliative dermatitis; fibromyalgia; focal glomerulosclerosis; giant cell arteritis; gout; gouty arthritis; graft-versus-host disease; hand eczema; Henoch-Schonlein purpura; herpes gestationis; hirsutism; hypersensitivity drug reactions; idiopathic cerato-scleritis; idiopathic pulmonary fibrosis; idiopathic thrombocytopenic purpura; inflammatory bowel or gastrointestinal disorders, inflammatory dermatoses; juvenile rheumatoid arthritis; laryngeal edema; lichen planus; Loeffler's syndrome; lupus nephritis; lupus vulgaris; lymphomatous tracheobronchitis; macular edema; multiple sclerosis; musculoskeletal and connective tissue disorder; myasthenia gravis; myositis; obstructive pulmonary disease; ocular inflammation; organ transplant rejection; osteoarthritis; pancreatitis; pemphigoid gestationis; pemphigus vulgaris; polyarteritis nodosa; polymyalgia rheumatica; primary adrenocortical insufficiency; primary billiary cirrhosis; pruritus scroti; pruritis/inflammation, psoriasis; psoriatic arthritis; Reiter's disease; relapsing polychondritis; rheumatic carditis; rheumatic fever; rheumatoid arthritis; rosacea caused by sarcoidosis; rosacea caused by scleroderma; rosacea caused by Sweet's syndrome; rosacea caused by systemic lupus erythematosus; rosacea caused by urticaria; rosacea caused by zoster-associated pain; sarcoidosis; scleroderma; segmental glomerulosclerosis; septic shock syndrome; serum sickness; shoulder tendinitis or bursitis; Sjogren's syndrome; Still's disease; stroke-induced brain cell death; Sweet's disease; systemic dermatomyositis; systemic lupus erythematosus; systemic sclerosis; Takayasu's arteritis; temporal arteritis; thyroiditis; toxic epidermal necrolysis; tuberculosis; type-1 diabetes; ulcerative colitis; uveitis; vasculitis; and Wegener's granulomatosis.

17. The method of claim 1 , wherein said immune disorder results from dysregulation of Toll-like receptor signaling or type I interferon-mediated immunity.

18. The method of claim 13 , wherein said retinoic acid compound and said second therapeutic compound are formulated together.

19. The method of claim 1 , wherein said immune disorder is selected from the group consisting of acne vulgaris; acute respiratory distress syndrome; Addison's disease; adrenocortical insufficiency; adrenogenital ayndrome; allergic conjunctivitis; allergic rhinitis; allergic intraocular inflammatory diseases, ANCA-associated small-vessel vasculitis; angioedema; aphthous stomatitis; atherosclerosis; atopic dermatitis; autoimmune hemolytic anemia; autoimmune hepatitis; Bell's palsy; berylliosis; bronchial asthma; bullous herpetiformis dermatitis; bullous pemphigoid; carditis; celiac disease; cerebral ischaemia; chronic obstructive pulmonary disease; cirrhosis; Cogan's syndrome; contact dermatitis; Cushing's syndrome; dermatomyositis; discoid lupus erythematosus; eosinophilic fasciitis; epicondylitis; erythema nodosum; exfoliative dermatitis; focal glomerulosclerosis; giant cell arteritis; gout; gouty arthritis; Henoch-Schonlein purpura; herpes gestationis; hirsutism; hypersensitivity drug reactions; idiopathic cerato-scleritis; idiopathic pulmonary fibrosis; idiopathic thrombocytopenic purpura; laryngeal edema; Loeffler's syndrome; lupus nephritis; lupus vulgaris; lymphomatous t

Assignees

• Lu Kun Ping
• Tun-Kyi Adrian
• Finn Greg
• Beth Israel Deaconess Medical Ct Inc

Inventors

• Lu Kun Ping
• Tun-Kyi Adrian
• Finn Greg

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/203 Primary

  Retinoic acids {; Salts thereof} · CPC title

• A61K31/522

  having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir · CPC title

• A61K31/47

  Quinolines; Isoquinolines · CPC title