Method to predict response to pharmacological chaperone treatment of diseases

Abstract

The present invention provides methods to determine whether a patient with a lysosomal storage disorder will benefit from treatment with a specific pharmacological chaperone. The present invention exemplifies an in vitro method for determining α-galactosidase A responsiveness to a pharmacological chaperone such as 1-deoxygalactonojirimycin in a cell line expressing a mutant from of α-galactosidase A. The invention also provides a method for diagnosing Fabry disease in patients suspected of having Fabry disease.

1 . A method for determining whether a patient expressing a mutant form of a protein will respond to treatment with a specific pharmacological chaperone for the protein, which method comprises a. contacting a first host cell with a pharmacological chaperone specific for the protein, wherein the first host cell expresses the mutant form of the protein; and b. comparing protein activity in a second host cell not contacted with the specific pharmacological chaperone, with protein activity in the first host cell contacted with the specific pharmacological chaperone, wherein an increase in protein activity in the first host cell contacted with the specific pharmacological chaperone compared to the activity of the protein expressed by the second host cell not contacted with the specific pharmacological chaperone indicates that the patient will respond to treatment with the specific pharmacological chaperone. 
     
     
         2 . The method of  claim 1 , wherein the mutant form of the protein is caused by a missense mutation in a gene encoding the protein. 
     
     
         3 . The method of  claim 1 , wherein the protein is an enzyme. 
     
     
         4 . The method of  claim 3 , wherein the enzyme is a lysosomal enzyme. 
     
     
         5 . The method of  claim 4 , wherein the patient has been diagnosed with a lysosomal storage disorder. 
     
     
         6 . The method of  claim 5 , wherein the lysosomal enzyme is .alpha.-galactosidase A and the lysosomal storage disorder is Fabry disease. 
     
     
         7 . The method of  claim 1 , wherein the specific pharmacological chaperone is 1-deoxygalactonojirimycin. 
     
     
         8 . A method for producing a treatment therapy table, wherein the treatment therapy table indicates if a specific pharmacological chaperone is an effective compound for increasing the activity of a mutant protein, which method comprises: a. contacting a first host cell with a pharmacological chaperone specific for the protein, wherein the first host cell expresses the mutant protein; b. comparing protein activity in the first host cell contacted with the specific pharmacological chaperone with protein activity in a second host cell, wherein the second host cell expresses the mutant protein and is not contacted with the specific pharmacological chaperone; and c. recording the result of step (b) in the treatment therapy table, wherein a specific pharmacological chaperone recorded in the treatment therapy table that increases the activity of the mutant protein in the first host cell compared to the activity of the mutant protein in the second cell is a specific pharmacological chaperone that can be used as a therapy for a patient who expresses the mutant protein.