Treatment of vascular, autoimmune and inflammatory diseases using low dosages of IMPDH inhibitors

Abstract

The disclosure provides methods and compositions for treating a vascular, autoimmune, and/or inflammatory disease, or a condition associated therewith, with a dose of an inosine monophosphate dehydrogenase (IMPDH) inhibitor effective to treat the vascular, autoimmune and/or inflammatory disease, or associated condition but that does not produce immunosuppression sufficient to reduce the risk of allograft rejection. These lower doses of the immunosuppressant avoid the adverse consequences of severe immunosuppression while providing effective treatment of the vascular, autoimmune and/or inflammatory disease.

1 . A method of treating a vascular, autoimmune and/or inflammatory disease, or a condition associated therewith, comprising administering to a human subject an amount of an IMPDH inhibitory compound selected from MPA, MMF, and combinations thereof that is effective to treat or reduce the risk of the vascular, autoimmune and/or inflammatory disease, or a condition associated therewith, but that does not produce immunosuppression sufficient to reduce the risk of allograft rejection.  
   
   
       2 . The method of  claim 1  in which the compound is MMF.  
   
   
       3 . The method of  claim 1  in which the daily amount of compound administered corresponds to a low dose.  
   
   
       4 . The method of  claim 1  in which the daily amount of compound administered corresponds to an extra-low dose.  
   
   
       5 . The method of  claim 1  in which the daily amount of compound administered corresponds to an ultra-low dose.  
   
   
       6 . The method of  claim 1  in which the disease is a vascular disease.  
   
   
       7 . The method of  claim 6  in which the vascular disease is atherosclerosis, coronary heart disease (CHD), cardiovascular disease (CVD), coronary artery disease (CAD), cerebrovascular disease, or peripheral vascular disease.  
   
   
       8 . The method of  claim 1  in which the disease is an autoimmune disease.  
   
   
       9 . The method of  claim 8  in which the autoimmune disease is systemic lupus erythematosus (SLE), multiple sclerosis (MS), diabetes mellitus, or rheumatoid arthritis (RA).  
   
   
       10 . The method of  claim 1  in which the condition treated is associated with autoimmune disease.  
   
   
       11 . The method of  claim 10  in which the condition associated with the autoimmune disease is atherosclerosis.  
   
   
       12 . The method of  claim 10  in which the condition associated with the autoimmune disease is an inflammatory condition.  
   
   
       13 . The method of  claim 1  in which the disease is an inflammatory disease.  
   
   
       14 . The method of  claim 13  in which the inflammatory disease is vasculitis, Crohn's disease, ulcerative colitis, or inflammatory bowel disease.  
   
   
       15 . The method of any one of claims  1 - 14  in which the compound is administered orally.  
   
   
       16 . The method of  claim 15  in which the compound is administered once per day.  
   
   
       17 . The method of  claim 15  in which the compound is administered twice per day.  
   
   
       18 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and an amount of an IMPDH inhibitory compound selected from MPA, MMF, and combinations thereof that is effective to achieve a low, extra-low or ultra-low daily dose when taken once or more per day.  
   
   
       19 . The pharmaceutical composition of  claim 18  which includes an amount of the compound effective to achieve a low, extra-low or ultra-low daily dose when taken once per day.  
   
   
       20 . The pharmaceutical composition of  claim 18  which includes an amount of the compound effective to achieve a low, extra-low or ultra-low daily dose when taken twice per day.  
   
   
       21 . The pharmaceutical composition of any one of claims  18 - 20  in which the compound is MMF.