Early detection of lysosomal storage disorders

Abstract

The present invention relates generally to lysosomal storage disorders and to diagnostic agents for their detection in humans and other animals. More particularly, the present invention is directed to the uses of the LSD markers Lamp-1, Lamp-2, Limp-II, 4-sulphatase, acid phosphatase (ACP), β-hexasaminidase or α-mannosidase, amongst others as diagnotic agents for the detection of many lysosomal storage disorders.

What is claimed is:  
     
         1 . A kit for detecting a lysosomal storage disorder (LSD), or monitoring the progress of the LSD, or monitoring the efficacy of treatment of the LSD, the kit comprising: 
 an antigen; and    a first antibody molecule that is capable of binding to the antigen,    wherein, the antigen comprises an LSD marker enzyme, protein or polypeptide, or an immunologically interactive derivative, homologue or analogue thereof.    
     
     
         2 . The kit according to  claim 1 , wherein the first antibody is a monoclonal antibody.  
     
     
         3 . The kit according to  claim 1 , wherein the first antibody is a polyclonal antibody.  
     
     
         4 . The kit according to  claim 1 , wherein the first antibody is labeled with a reporter molecule.  
     
     
         5 . The kit according to  claim 4 , wherein the reporter molecule is an enzyme, flouophore or radionuclide molecule.  
     
     
         6 . The kit according to  claim 5 , wherein the enzyme, fluorophore or radionuclide molecule is selected from the list comprising horseradish peroxidase, glucose oxidase, β-galactosidase, alkaline phosphatase, fluorescein, Eu 3+  or other lanthanide metal or rhodamine.  
     
     
         7 . The kit according to  claim 6 , wherein the fluorophore molecule is Eu 3+ .  
     
     
         8 . The kit according to  claim 1 , further comprising a second antibody molecule that recognizes the first antibody, wherein the second antibody is conjugated to a reporter molecule.  
     
     
         9 . The kit according to  claim 8 , wherein the reporter molecule is an enzyme, flurophore or radionuclide molecule.  
     
     
         10 . The kit according to  claim 9 , wherein the enzyme, fluorophore or radionuclide molecule is selected from a list comprising horseradish peroxidase, glucose oxidase, β-galactosidase, alkaline phosphatase, fluorescein, Eu 3+  or there lanthanide metal or rhodamine.  
     
     
         11 . The kit according to  claim 10 , wherein the fluorophore molecule is Eu 3+ .  
     
     
         12 . The kit according to  claim 9 , wherein, if the reporter molecule is an enzyme, the kit further comprises a substrate molecule specific for the enzyme.  
     
     
         13 . The kit according to  claim 1 , wherein the antigen is a lysosomal-enzyme, -polypeptide or -protein or an immunologically interactive homologue, analogue or derivative thereof.  
     
     
         14 . The kit according to  claim 13 , wherein the lysosomal-enzyme, -polypeptide, -protein, or the immunologically interactive homologue, analogue or derivative thereof is selected from a list comprising Lamp-1, Lamp-2, Limp-II, mannose-6-phosphate receptor, α-L-iduronidase, 4-sulphatase, acid phosphatase (ACP), β-hexosaminidase, and α-mannosidase.  
     
     
         15 . The kit according to  claim 14 , wherein the antigen is Lamp-1 or the immunologically interactive derivative, homologue, or analogue thereof.  
     
     
         16 . The kit according to  claim 14 , wherein the antigen is Lamp-2 or the immunologically interactive derivative, homologue, or analogue thereof.  
     
     
         17 . The kit according to claim  30 , wherein the LSD is selected from a list set forth in Table 1.  
     
     
         18 . The kit according to  claim 17 , wherein the LSD is selected from a list comprising MPS I, MPS II, Gaucher disease, Pompe disease and Salla's disease.  
     
     
         19 . An isolated lysosomal storage disorder (“LSD”)-marker enzyme, -protein or polypeptide or an -immunologically interactive homologue, -analogue or derivative thereof when used for a method of detecting a LSD, monitoring the progress of a LSD or monitoring the efficacy of treatment of a LSD in a human or animal subject, the method comprising assaying the level of the LSD-marker enzyme, -protein, prolypeptide, or the -immunologically interactive homologue, -analogue or derivative thereof with a biological sample derived from the subject, wherein the biological sample is a blood, serum, plasma or urine sample.  
     
     
         20 . The isolated LSD marker according to  claim 19 , selected from a list comprising Lamp-1, Lamp-2, Limp-II, mannose-6-phosphate receptor, α-L-iduronidase, 4-sulphatase, acid phosphatase (ACP), β-hexosaminidase and α-mannosidase.  
     
     
         21 . The isolated LSD marker according to  claim 20 , further defined as Lamp-1.  
     
     
         22 . The isolated LSD marker according to  claim 20 , further defined as Lamp-2.