Method to predict response to pharmacological chaperone treatment of diseases
AssigneeAmicus Therapeutics, Inc.
InventorsElfrida Benjamin, Hung V. Do, Xiaoyang Wu, John Flanagan, Brandon Wustman
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Abstract
The present invention provides methods to determine whether a patient with a lysosomal storage disorder win 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.
Claims10
A method for identifying candidate patients having Fabry Disease for drug therapy, said method comprising:
- (a) identifying the mutant α-galactosidase A expressed in the patient having Fabry Disease,
- (b) expressing a recombinant form of said mutant α-galactosidase A in a host cell that does not naturally express the mutant α-galactosidase A and contacting this host cell with 1-deoxygalactonojirimycin;
- (c) determining the α-galactosidase A activity of the mutant α-galactosidase A in the host cell, and
- (d) comparing the α-galactosidase A activity determined in (c) to the α-galactosidase A in a the host cell when it is not contacted with 1-deoxygalactonojirimycin, and
- (e) determining that the patient is a candidate for treatment with 1-deoxygalactonojirimycin if:
- (i) in step (d) there is a 1.3 to 40 fold increase in α-galactosidase A activity in the host cell contacted with 1-deoxygalactonojirimycin when compared to α-galactosidase A activity in the host cell not contacted with 1-deoxygalactonojirimycin, or
- (ii) the α-galactosidase A activity in the host cell is at least 2% to about 100% activity of a non-mutant α-galactosidase A.
A method for treating a patient diagnosed with Fabry Disease, said method comprising administering to the patient a therapeutically effective dose of 1-deoxygalactonojirimycin, wherein the patient is identified as being a candidate for treatment with 1-deoxygalactonojirimycin by the method comprising:
- (a) identifying the mutant α-galactosidase A expressed in the patient having Fabry Disease,
- (b) expressing a recombinant form of said mutant α-galactosidase A in a host cell that does not naturally express the mutant α-galactosidase A and contacting this host cell with 1-deoxygalactonojirimycin;
- (c) determining the α-galactosidase A activity of the mutant α-galactosidase A in the host cell,
- (d) comparing the α-galactosidase A activity determined in (c) to the α-galactosidase A in a host cell when it is not contacted with 1-deoxygalactonojirimycin, and
- (e) determining that the patient is a candidate for treatment with 1-deoxygalactonojirimycin if:
- (i) in step (d) there is a 1.3 to 40 fold increase in α-galactosidase A activity in the host cell contacted with 1-deoxygalactonojirimycin when compared to α-galactosidase A activity in the host cell not contacted with 1-deoxygalactonojirimycin, or
- (ii) the α-galactosidase A activity in the host cell is at least 2% to about 100% activity of a non-mutant α-galactosidase A.
Dependencies are inferred from the claim text.