Methods and compositions for treatment of gaucher disease via modulation of c5a receptor

Abstract

Disclosed are compositions and methods for the reduction of C5a mediated immune inflammation. The methods, in various aspects, may include the step of administering a C5aR antagonist to a subject in need of such treatment. In one aspect, the subject in need may have a lysosomal acid storage disease. Therapeutic kits and articles of manufacture are also disclosed.

1 . A composition comprising a C5aR antagonist for the treatment of a lysosomal storage disease. 
     
     
         2 . The composition according to  claim 1 , wherein said C5aR antagonist is an A8 Δ71-73  peptide. 
     
     
         3 . The composition of  claim 1 , wherein said composition decreases C5a mediated immune inflammation. 
     
     
         4 . The composition of  claim 1  wherein said treatment results in reduced inflammation in a sequestered site selected from the blood and/or brain. 
     
     
         5 . A method of reducing C5a mediated immune inflammation, comprising the step of administering the composition of  claim 1 , in an amount sufficient to reduce inflammation in a tissue of interest. 
     
     
         6 . The method of  claim 5 , wherein said reduction of C5a mediated immune inflammation is in a patient having a lysosomal storage disease. 
     
     
         7 . The method according to  claim 5 , wherein said reduction of C5a mediated immune inflammation is in a patient having a lysosomal storage disease selected from globoid cell leukodystrophy, GM2 gangliosidosis, Niemann-Pick C, mucopolysaccharidoses, Fabry, Tay-Sachs, Sandhoff, Hypercholesterolemia, Gaucher's Disease, and combinations thereof. 
     
     
         8 . The method of  claim 5 , wherein said subject has one or more signs of clinical Gaucher disease manifestation selected from hepatosplenomegaly, anemia, thrombocytopenia, bone defects, or a combination thereof. 
     
     
         9 . The method of  claim 5 , wherein said C5aR antagonist is administered in an amount sufficient to reduce inflammation in a tissue of interest. 
     
     
         10 . The method of  claim 5 , wherein said C5aR antagonist is administered in an amount sufficient to reduce complement activation. 
     
     
         11 . The method of  claim 5 , wherein said C5aR antagonist is administered in an amount sufficient to reduce circulating levels of inflammatory cytokines and chemokines. 
     
     
         12 . The method of  claim 5 , wherein said administration step is carried out before, after, or during a second treatment, wherein said treatment is selected from substrate reduction therapy, gene therapy, substrate reduction therapy, enzyme replacement products, or a combination thereof. 
     
     
         13 . A therapeutic kit comprising: (i) the composition according to  claim 1 ; and (ii) means for delivery of the composition to a human. 
     
     
         14 . An article of manufacture comprising:
 a container comprising a label; and   a composition comprising: (i) the composition according to  claim 1 , wherein the label indicates that the composition is to be administered to a human having, suspected of having, or at risk for developing, a lysosomal storage disease.   
     
     
         15 . The method of  claim 9 , wherein said tissue of interest is blood or brain or both.