Methods of treating fibrosing diseases by induction of immune tolerance

Abstract

The present invention has demonstrated for the first time that orally administered type I collagen (CI) induced tolerance to CI in patients suffering from systemic sclerosis (SSc) and ameliorated clinical manifestations of the disease. Accordingly, the present invention provides methods of treating a fibrosing disease by oral administration of a tissue protein, for example, collagen, derived from the tissue undergoing fibrosis.

1 . A method for treating a fibrosing disease in a patient, comprising orally administering to the patient one or more collagen fragments, said collagen fragments selected from the group consisting of: α1(I) CB1, CB2, CB3, CB4, CB5, CB6, CB7, CB8 and α2(I) CB1, CB2, CB3, CB4 and CB5. 
   
   
       2 . The method of  claim 1 , wherein said fibrosing disease is selected from the group consisting of skin fibrosis, liver cirrhosis, renal fibrosis, lung fibrosis, heart fibrosis, gastrointestinal fibrosis and vascular fibrosis. 
   
   
       3 . The method of  claim 1 , wherein said patient has been suffering from said fibrosing disease for at least 3 years. 
   
   
       4 . The method of  claim 1 , wherein said collagen is derived from human or an animal species other than human. 
   
   
       5 . The method of  claim 1 , wherein said collagen is orally administered to said patient at about 500 μg/day. 
   
   
       6 . The method of  claim 1 , wherein the patient is treated for about 12 months. 
   
   
       7 . The method of  claim 1 , wherein the patient is treated for about 36 months. 
   
   
       8 . The method of  claim 1 , wherein the oral administration of said collagen induces tolerance in said patient. 
   
   
       9 . A dosage form for oral administration for treating a fibrosing disease in a patient, comprising one or more collagen fragments, said collagen fragments selected from the group consisting of: α(I) CB2, CB3, CB4, CB5, CB6, CB7, CB8, and α2(I) CB0, CB1, CB2, CB3, CB4 and CB5. 
   
   
       10 . The dosage form of  claim 9 , wherein said dosage form is adapted for daily administration. 
   
   
       11 . The dosage form of  claim 9 , wherein said one or more collagen fragments is adapted to induced tolerance in said patient upon oral administration. 
   
   
       12 . The dosage form of  claim 9 , wherein said dosage form is orally administered to a patient at about 500 μg/day.