Lipid hydrolysis therapy for atherosclerosis and related diseases

Abstract

The present invention comprises a method to diminish and/or eliminate atherosclerotic plaques, in mammals, through direct and indirect treatment of these plaques, in situ, using suitable substances which are capable of lipid removal, primarily through hydrolysis, either by a catalytic or stoichiometric process, wherein the substance targets receptors in and/or on the cell which lead to uptake into the lysosome. Such substances used to diminish and/or eliminate atherosclerotic plaques are generally comprised of lipid hydrolyzing proteins and/or polypeptides.

What is claimed is: 
     
         1 . A method for treating an individual having a lysosomal acid lipase (LAL) deficiency comprising administering to said individual a safe and effective amount of a composition comprising a protein or peptide having at least 85% sequence homology to human lysosomal acid lipase and a pharmaceutically acceptable carrier;
 wherein said LAL has six N-linked acetylglycosylation sites; and   wherein said administration step is carried out via an intravenous infusion of said composition.   
     
     
         2 - 7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein said LAL comprises a protein having a Ser 153  residue. 
     
     
         9 . The method of  claim 1 , wherein said LAL comprises a substitution of amino acid Pro(−6) to Thr and Gly2 to Arg. 
     
     
         10 - 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein said LAL comprises an N-acetylglycosylation residue that is oligosaccharide-terminated. 
     
     
         13 . The method of  claim 1 , wherein said lysosomal acid lipase comprises an oligosaccharide terminating mannose residue 
     
     
         14 - 68 . (canceled) 
     
     
         69 . The method of  claim 1 , wherein said administration step results in biological activity of said LAL in said individual. 
     
     
         70 . The method of  claim 1 , wherein said administration step results in a decrease of cholesterol and triglycerides in the liver. 
     
     
         71 . The method of  claim 1 , wherein said LAL activity causes a reduction in the size and number of lipid filled Kupffer cells in the liver. 
     
     
         72 . The method of  claim 1 , wherein said administration causes a reduction in hepatosplenomegaly. 
     
     
         73 . The method of  claim 1 , wherein said LAL activity causes a reduction in the size and number of macrophage storage cells in the liver. 
     
     
         74 . The method of  claim 1 , wherein said administration step results in a decrease of cholesterol and triglycerides in the small intestine. 
     
     
         75 . The method of  claim 1 , wherein said administration step results in LAL activity in the small intestine. 
     
     
         76 . The method of  claim 1 , wherein said administration step results in a decrease of cholesterol and triglycerides in the spleen. 
     
     
         77 . The method of  claim 1 , wherein said pharmaceutically acceptable carrier is an aqueous isotonic sterile injectable solution. 
     
     
         78 . The method of  claim 1 , wherein said composition comprises a buffer. 
     
     
         79 . The method of  claim 1 , wherein said composition comprises a bacteriostat. 
     
     
         80 . The method of  claim 1 , wherein said composition comprises a stabilizer. 
     
     
         81 . The method of  claim 1 , wherein said composition comprises at least one of anti-oxidant, buffer, bacteriostat, preservative, or stabilizer.