Application of pcsk9 inhibitors in the preparation of drugs for the treatment of inflammatory and immune diseases

Abstract

The invention belongs to the biopharmaceutical. It involves the role and mechanism of PCSK9 in inflammatory immune diseases, and the application of PCSK9 inhibitors to the preparation of drugs for the treatment of inflammatory immune diseases mediated by T cells. In particular, it involves the use of PCSK9 monoclonal antibody, PCSK9 interference RNA and PCSK9 small molecule inhibitors for treating psoriasis, atopic dermatitis, or urticaria. The invention uses psoriasis as an embodiment for the study of inflammatory and immune diseases. It is found that PCSK9 plays an important role in the treatment of inflammatory immune diseases. The PCSK9 monoclonal antibody, PCSK9 interference RNA, and PCSK9 small molecule inhibitor can be further developed for treating inflammatory immune-diseases, such as psoriasis with fewer adverse reactions, at low cost, and with good efficacy.

1 . A method of treating an inflammatory immune disease by administration of a therapeutically effective amount of a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor selected from the group consisting of PCSK9 monoclonal antibodies, PCSK9 small molecule interfering RNAs, and a PCSK9 vaccine, and the inflammatory immune disease is selected from the group consisting of psoriasis, psoriatic arthritis, eczema, atopic dermatitis, urticaria, glucocorticoid dependent dermatitis, rheumatoid arthritis, scleroderma, diabetes, chronic liver disease, and lymphoma. 
     
     
         2 . The method of  claim 1 , wherein the PCSK9 inhibitor is one or more of the PCSK9 monoclonal antibodies. 
     
     
         3 . The method of  claim 2 , wherein the inflammatory immune disease is psoriasis, atopic dermatitis or urticaria, and the PCSK9 inhibitor is topically, systemically or subcutaneously administered. 
     
     
         4 . The method of  claim 3 , wherein the inflammatory immune disease is psoriasis. 
     
     
         5 . The method of  claim 3 , wherein the PCSK9 inhibitor is administered once per day. 
     
     
         6 . The method of  claim 2 , wherein the PCSK9 inhibitor is topically administered. 
     
     
         7 . The method of  claim 5 , wherein the PCSK9 monoclonal antibodies are administered as an ointment in a concentration of 0.001-0.05%. 
     
     
         8 . The method of  claim 1 , wherein the PCSK9 inhibitor is one or more of the small molecule interference RNAs. 
     
     
         9 . The method of  claim 8 , wherein the one or more small molecule interference RNAs significantly inhibit abnormal proliferation of human keratinocytes and promote their apoptosis through an NFkb pathway. 
     
     
         10 . The method of  claim 8 , wherein the inflammatory immune disease is selected from the group consisting of psoriasis, psoriatic arthritis, eczema, atopic dermatitis, urticaria, glucocorticoid dependent dermatitis, and scleroderma. 
     
     
         11 . The method of  claim 10 , wherein the therapeutically effective amount of the PCSK9 inhibitor is administered topically. 
     
     
         12 . The method of  claim 11 , wherein the PCSK9 inhibitor is administered as a cream or ointment containing the PCSK9 inhibitor in a concentration of 0.001-0.05%. 
     
     
         13 . The method of  claim 11 , wherein the PCSK9 inhibitor is administered once per day. 
     
     
         14 . The method of  claim 8 , wherein the therapeutically effective amount of the PCSK9 inhibitor is administered subcutaneously. 
     
     
         15 . The method of  claim 14 , wherein the PCSK9 inhibitor is administered at a concentration of 8 mg/kg or in a dose of 5 mg. 
     
     
         16 . The method of  claim 8 , wherein the PCSK9 inhibitor is administered subcutaneously, topically or systemically. 
     
     
         17 . The method of  claim 16 , wherein the PCSK9 inhibitor is administered (i) topically as a cream or ointment containing the PCSK9 inhibitor in a concentration of 0.001-0.05% or (ii) subcutaneously at a concentration of 8 mg/kg or in a dose of 5 mg. 
     
     
         18 . The method of  claim 1 , wherein the PCSK9 inhibitor is a PCSK9 vaccine. 
     
     
         19 . The method of  claim 18 , wherein the therapeutically effective amount of the PCSK9 inhibitor is administered subcutaneously.