Use of serine protease inhibitors in the treatment of skin diseases

Abstract

This invention relates to therapeutic compounds which are inhibitors of serine proteases, to pharmaceutical compositions thereof and to their use in the treatment of the human or animal body. More specifically, the present invention relates to a method for the treatment, diagnosis or prognosis of skin diseases comprising the administration to a subject in need thereof of a therapeutically effective amount of a Serine protease inhibitor.

1 . Use of a recombinant Serine protease inhibitor selected from the group consisting in SEQ ID No 2, SEQ ID No 4, SEQ ID No 6, SEQ ID No 8, SEQ ID No 10, SEQ ID No 12, SEQ ID No 14, SEQ ID No 39, SEQ ID No 40, SEQ ID No 41, SEQ ID No 42, SEQ ID No 43, SEQ ID No 44, SEQ ID No 45, SEQ ID No 46, SEQ ID No 47, SEQ ID No 49, SEQ ID No 50, SEQ ID No 51, SEQ ID No 52, SEQ ID No 53, SEQ ID No 54, SEQ ID No 55, SEQ ID No 56, SEQ ID No 57, SEQ ID No 58 and SEQ ID No 59, or a biologically active fragment thereof having a Serine protease inhibitor activity, in the preparation of a medicament for the treatment of a skin disease. 
     
     
         2 . Use according to  claim 1 , wherein the Serine protease is selected from the group comprising kallikrein, plasmin, chymotrypsin (Chtr), urokinase (uPA), tryptase and neutrophile elastase (HNE) enzymes and/or a combination thereof. 
     
     
         3 . Use according to  claim 2 , wherein the kallikrein is selected from the group comprising hK2, hK3, hK4, hK5, hK6, hK7, hK8, hK9 hK10, hK11, hK12, hK13, hK14 or hK15 and/or a combination thereof. 
     
     
         4 . Use according to  claim 3 , wherein the kallikrein is selected from the group comprising hK2, hK5, hK7, and hK14 and/or a combination thereof. 
     
     
         5 . Use according to  claim 1 , wherein the skin disease is selected from the group comprising Netherton syndrome, Atopic Dermatitis, Psoriasis and Peeling Skin Syndrome. 
     
     
         6 . Use according to  claim 5 , wherein the skin disease is Netherton syndrome. 
     
     
         7 . A method for treating or preventing a skin disease in a mammal comprising administering to said mammal a pharmaceutical composition comprising a recombinant Serine protease inhibitor selected from the group consisting in SEQ ID No 2, SEQ ID No 4, SEQ ID No 6, SEQ ID No 8, SEQ ID No 10, SEQ ID No 12, SEQ ID No 14, SEQ ID No 39, SEQ ID No 40, SEQ ID No 41, SEQ ID No 42, SEQ ID No 43, SEQ ID No 44, SEQ ID No 45, SEQ ID No 46, SEQ ID No 47, SEQ ID No 49, SEQ ID No 50, SEQ ID No 51, SEQ ID No 52, SEQ ID No 53, SEQ ID No 54, SEQ ID No 55, SEQ ID No 56, SEQ ID No 57, SEQ ID No 58 and SEQ ID No 59, or a biologically active fragment thereof, having a Serine protease inhibitor activity. 
     
     
         8 . The method of  claim 7 , wherein the Serine protease is selected from the group comprising kallikrein, plasmin, chymotrypsin (Chtr), urokinase (uPA), tryptase and neutrophile elastase (HNE) enzymes and/or a combination thereof. 
     
     
         9 . The method according to  claim 8 , wherein the kallikrein is selected from the group comprising hK2, hK3, hK4, hK5, hK6, hK7, hK8, hK9 hK10, hK11, hK12, hK13, hK14 or hK15 and/or a combination thereof. 
     
     
         10 . The method of  claim 9 , wherein the kallikrein is selected from the group comprising hK2, hK5, hK7, and hK14 and/or a combination thereof. 
     
     
         11 . The method of  claim 10 , wherein the skin disease is selected from the group comprising Netherton syndrome, Atopic dermatitis, Psoriasis and Peeling Skin Syndrome. 
     
     
         12 . The method of  claim 11 , wherein the skin disease is Netherton syndrome. 
     
     
         13 . A kit for the treatment or prevention of a skin disease comprising a recombinant serine protease selected from the group consisting in SEQ ID No 2, SEQ ID No 4, SEQ ID No 6, SEQ ID No 8, SEQ ID No 10, SEQ ID No 12, SEQ ID No 14, SEQ ID No 39, SEQ ID No 40, SEQ ID No 41, SEQ ID No 42, SEQ ID No 43, SEQ ID No 44, SEQ ID No 45, SEQ ID No 46, SEQ ID No 47, SEQ ID No 49, SEQ ID No 50, SEQ ID No 51, SEQ ID No 52, SEQ ID No 53, SEQ ID No 54, SEQ ID No 55, SEQ ID No 56, SEQ ID No 57, SEQ ID No 58 and SEQ ID No 59, optionally with reagents and/or instructions for use. 
     
     
         14 . A cosmetic composition for the improvement of an undesirable skin condition comprising a pharmaceutically effective amount of a recombinant serine protease inhibitor selected from the group consisting in SEQ ID No 2, SEQ ID No 4, SEQ ID No 6, SEQ ID No 8, SEQ ID No 10, SEQ ID No 12, SEQ ID No 14, SEQ ID No 39, SEQ ID No 40, SEQ ID No 41, SEQ ID No 42, SEQ ID No 43, SEQ ID No 44, SEQ ID No 45, SEQ ID No 46, SEQ ID No 47, SEQ ID No 49, SEQ ID No 50, SEQ ID No 51, SEQ ID No 52, SEQ ID No 53, SEQ ID No 54, SEQ ID No 55, SEQ ID No 56, SEQ ID No 57, SEQ ID No 58 and SEQ ID No 59, or a biologically active fragment thereof having a Serine protease inhibitor activity. 
     
     
         15 . The cosmetic composition according to  claim 14 , wherein the Serine protease is selected from the group comprising kallikrein, plasmin, chymotrypsin (Chtr), urokinase (uPA), tryptase and neutrophile elastase (HNE) enzymes and/or a combinaison thereof. 
     
     
         16 . The method according to  claim 15 , wherein the kallikrein is selected from the group comprising hK2, hK3, hK4, hK5, hK6, hK7, hK8, hK9 hK10, hK11, hK12, hK13, hK14 or hK15 and/or a combination thereof. 
     
     
         17 . The cosmetic composition according to  claim 16 , wherein the kallikrein is selected from the group comprising hK2, hK5, hK7, and hK14 and/or a combinaison thereof. 
     
     
         18 . Use of a recombinant Serine protease inhibitor selected from the group consisting in SEQ ID No 2, SEQ ID No 4, SEQ ID No 6, SEQ ID No 8, SEQ ID No 10, SEQ ID No 12, SEQ ID No 14, SEQ ID No 39, SEQ ID No 40, SEQ ID No 41, SEQ ID No 42, SEQ ID No 43, SEQ ID No 44, SEQ ID No 45, SEQ ID No 46, SEQ ID No 47, SEQ ID No 49, SEQ ID No 50, SEQ ID No 51, SEQ ID No 52, SEQ ID No 53, SEQ ID No 54, SEQ ID No 55, SEQ ID No 56, SEQ ID No 57, SEQ ID No 58 and SEQ ID No 59, or a biologically active fragment thereof, in the preparation of cosmetic composition for the improvement of an undesirable skin condition. 
     
     
         19 . A detection assay for the diagnosis or prognosis of a skin disease in a tissue sample comprising contacting the tissue sample with a recombinant serine protease inhibitor selected from the group consisting in SEQ ID No 2, SEQ ID No 4, SEQ ID No 6, SEQ ID No 8, SEQ ID No 10, SEQ ID No 12, SEQ ID No 14, SEQ ID No 39, SEQ ID No 40, SEQ ID No 41, SEQ ID No 42, SEQ ID No 43, SEQ ID No 44, SEQ ID No 45, SEQ ID No 46, SEQ ID No 47, SEQ ID No 49, SEQ ID No 50, SEQ ID No 51, SEQ ID No 52, SEQ ID No 53, SEQ ID No 54, SEQ ID No 55, SEQ ID No 56, SEQ ID No 57, SEQ ID No 58 and SEQ ID No 59 and having a detected label, determining and measuring the amount of said detected label and correlating this amount to the presence or absence of a disease in said tissue sample. 
     
     
         20 . Use according to  claim 2 , wherein the skin disease is selected from the group comprising Netherton syndrome, Atopic Dermatitis, Psoriasis and Peeling Skin Syndrome. 
     
     
         21 . Use according to  claim 3 , wherein the skin disease is selected from the group comprising Netherton syndrome, Atopic Dermatitis, Psoriasis and Peeling Skin Syndrome. 
     
     
         22 . Use according to  claim 4 , wherein the skin disease is selected from the group comprising Netherton syndrome, Atopic Dermatitis, Psoriasis and Peeling Skin Syndrome.