Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency

Abstract

The invention relates to dose escalation enzyme replacement therapy using acid sphingomyelinase (ASM) for the treatment of human subjects having acid sphingomyelinase deficiency (ASMD), and, in particular, patients with non-neurological manifestations of Niemann-Pick Disease (NPD), and in certain embodiments, NPD type B.

1 .- 19 . (canceled) 
     
     
         20 . A method for treating an acid sphingomyelinase deficiency (ASMD), comprising:
 a. administering to a human subject in need thereof one or more doses of 0.1 mg/kg recombinant human acid sphingomyelinase (rhASM); and   b. administering sequentially escalating higher doses of rhASM to the human subject if the subject does not manifest one or more moderate or severe adverse events, wherein the higher doses are from 0.1 mg/kg to 0.5 mg/kg or 0.1 to 1 mg/kg higher than the previous dose.   
     
     
         21 . The method of  claim 20 , wherein each dose is administered two weeks after the previous dose. 
     
     
         22 . The method of  claim 20 , wherein the doses are administered intravenously. 
     
     
         23 . The method of  claim 21 , wherein the doses are administered intravenously. 
     
     
         24 . The method of  claim 20 , wherein the ASMD is Niemann Pick Disease (NPD) type B. 
     
     
         25 . The method of  claim 21 , wherein the ASMD is Niemann Pick Disease (NPD) type B. 
     
     
         26 . The method of  claim 22 , wherein the ASMD is Niemann Pick Disease (NPD) type B. 
     
     
         27 . The method of  claim 23 , wherein the ASMD is Niemann Pick Disease (NPD) type B. 
     
     
         28 . The method of  claim 20 , wherein the human subject is a human adult. 
     
     
         29 . The method of  claim 21 , wherein the human subject is a human adult. 
     
     
         30 . The method of  claim 22 , wherein the human subject is a human adult. 
     
     
         31 . The method of  claim 23 , wherein the human subject is a human adult. 
     
     
         32 . The method of  claim 24 , wherein the human subject is a human adult. 
     
     
         33 . The method of  claim 25 , wherein the human subject is a human adult. 
     
     
         34 . The method of  claim 26 , wherein the human subject is a human adult. 
     
     
         35 . The method of  claim 27 , wherein the human subject is a human adult. 
     
     
         36 . The method of  claim 20 , which further comprises administering a maintenance dose to the human subject. 
     
     
         37 . The method of  claim 36 , wherein the maintenance dose is administered every two weeks. 
     
     
         38 . The method of  claim 36 , wherein the maintenance dose is the highest dose tolerated.