Treatment of pompe's disease

Abstract

The invention provides methods of treating Pompe's disease using human acid alpha glucosidase. A preferred treatment regime comprises administering greater than 10 mg/kg body weight per week to a patient.

What is claimed is:  
     
         1 . A method of treating a patient with Pompe's disease, comprising: administering to the patient a therapeutically effective amount of human acid alpha glucosidase.  
     
     
         2 . The method of  claim 1 , wherein the patient is administered at least 10 mg/kg body weight per week.  
     
     
         3 . The method of  claim 1 , wherein the patient is administered at least 60 mg/kg body weight per week.  
     
     
         4 . The method of  claim 1 , wherein the patient is administered at least 120 mg/kg body weight per week.  
     
     
         5 . The method of any of claims  1 - 4 , wherein the patient is administered a single dosage of alpha-glucosidase per week.  
     
     
         6 . The method of any of claims  1 - 4 , wherein the patient is administered three dosages of alpha-glucosidase per week.  
     
     
         7 . The method of any of claims  1 - 4 , wherein the amount is administered per week for a period of at least 24 weeks.  
     
     
         8 . The method of  claim 1 , wherein the alpha-glucosidase is administered intravenously.  
     
     
         9 . The method of  claim 1 , wherein the alpha-glucosidase was produced in milk of a transgenic mammal.  
     
     
         10 . The method of  claim 1 , wherein the patient has infantile Pompe's disease.  
     
     
         11 . The method of  claim 10 , wherein the patient survives to be at least one year old.  
     
     
         12 . The method of  claim 1 , wherein the patient has juvenile Pompe's disease.  
     
     
         13 . The method of  claim 1 , wherein the patient has adult Pompe's disease.  
     
     
         14 . The method of  claim 1 , wherein the alpha-glucosidase is predominantly in a 110 kD form.  
     
     
         15 . The method of  claim 1 , further comprising monitoring a level of human acid alpha glucosidase in the patient.  
     
     
         16 . The method of  claim 15 , further comprising administering a second dosage of human acid alpha glucosidase if the level of alpha-glucosidase falls below a threshold value in the patient.  
     
     
         17 . The method of  claim 1 , wherein the human alpha glucosidase is administered intravenously and the rate of administration increases during the period of administration.  
     
     
         18 . The method of  claim 17 , wherein the rate of administration increases by at least a factor of ten during the period of administration.  
     
     
         19 . The method of  claim 17 , wherein the rate of administration increases by at least a factor of ten within a period of five hours.  
     
     
         20 . The method of  claim 17 , wherein the patient is administered a series of at least four dosages, each dosage at a higher strength than the previous dosage.  
     
     
         21 . The method of  claim 20 , wherein the dosages are a first dosage of 0.03-3 mg/kg/hr, a second dosage of 0.3-12 mg/kg/hr, a third dosage of 1-30 mg/kg/hr and a fourth dosage of 2-60 mg/kg/hr.  
     
     
         22 . The method of  claim 21 , wherein the dosages are a first dosage of 0.1-1 mg/kg/hr, a second dosage of 1-4 mg/kg/hr, a third dosage of 3-10 mg/kg/hr and a fourth dosage of 6-20 mg/kg/hr.  
     
     
         23 . The method of  claim 22 , wherein the dosages are a first dosage of 0.25-4 mg/kg/hr, a second dosage of 0.9-1.4 mg/kg/hr, a third dosage of 3.6-5.7 mg/kg/hr and a fourth dosage of 7.2-11.3 mg/kg/hr.  
     
     
         24 . The method of  claim 23 , wherein the dosages are a first dosage of 0.3 mg/kg/hr, a second dosage of 1 mg/kg/hr, a third dosage of 4 mg/kg/hr and a fourth dosage of 12 mg/kg/hr.  
     
     
         25 . The method of any of claims  20 - 24 , wherein the first, second, third and fourth dosages are each administered for periods of 15 min to 8 hours.  
     
     
         26 . The method of any of claims  20 - 24 , wherein the first, second, third and fourth dosages are administered for periods of 1 hr, 1 hr, 0.5 hr and 3 hr respectively.  
     
     
         27 . A pharmaceutical composition comprising human acid alpha glucosidase, human serum albumin, and a sugar in a physiologically acceptable buffer in sterile form.  
     
     
         28 . The pharmaceutical composition of  claim 17  comprising human acid alpha glucosidase, human serum albumin, and glucose in sodium phosphate buffer.  
     
     
         29 . A pharmaceutical composition comprising alpha glucosidase, mannitol and sucrose in an aqueous solution.  
     
     
         30 . The pharmaceutical composition of  claim 27 , wherein the sugar comprises mannitol and sucrose and the concentration of mannitol is 1-3% w/w of the aqueous solution and the concentration of sucrose is 0.1 to 1% w/w of the aqueous solution.  
     
     
         31 . The pharmaceutical composition of  claim 27 , wherein the concentration of mannitol is 2% w/w and the concentration of sucrose is 0.5% w/w.  
     
     
         32 . A lyophilized composition produced by lyophilizing a pharmaceutical composition comprising human acid glucosidase, mannitol and sucrose in aqueous solution.  
     
     
         33 . A pharmaceutical composition prepared by 
 lyophilizing a first composition comprising human acid alpha-glucosidase, mannitol, sucrose and an aqueous solution to produce a second composition; and reconstituting the lyophilized composition in saline to produce a third composition.    
     
     
         34 . The pharmaceutical composition of  claim 33 , wherein 
 the human acid alpha-glucosidase is at 5 mg/ml in both the first and third composition, the mannitol is at 2 mg/ml in the first composition, the sucrose is at 0.5 mg/ml in the first composition, and the saline used in the reconstituting step is 0.9% w/w.