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US 9,066,939 B2Granted
Urinary triaosylceramide (GB3) as a marker of cardiac disease
AssigneeBaylor Research Institute
InventorsRaphael Schiffmann, Fanny Mochel, Lawrence Sweetman, Sabrina Forni
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Abstract
The present invention describes a method for determination of urinary globotriaosylceramide (Gb3) levels in non-Fabry disease cardiac patients. Determination of Gb3 levels provides a screening method for determining cardiac risk and may offer an alternative therapeutic option for cardiac disease management or cardiac disease risk mitigation by lowering Gb3 levels by the use of pharmacological chaperones or other agents.
Claims15
A method of treating cardiac disease in a human subject, comprising:
- obtaining and placing a urine sample from the human subject on a filter paper;
- drying the urine sample on the filter paper;
- extracting the dried urine sample with methanol;
- injecting a portion of the extracted urine sample into a LC-MS system along with a radio-labeled standard solution comprising a known concentration of the Gb3 in methanol;
- eluting the Gb3 in the urine sample and the standard solution with a methanol/water gradient;
- obtaining one or more peaks of the Gb3 in the urine sample and the standard solution in a mass spectrum from the LC-MS system;
- creating a calibration curve by plotting a peak area of the one or more peaks of Gb3 in the biological sample and the standard solutions against a retention time;
- calculating the level of the Gb3 in the urine sample by calculating a concentration of the Gb3 from the calibration curve;
- and
- if said calculated level of Gb3 in the urine sample is above 200 ng/ml, administering a pharmacological or chemical chaperone to the patient in a sufficient concentration to treat cardiac disease, wherein the human subject is selected from a healthy human subject, a non-Fabry disease patient, and a subject with no genetic predispositions towards Fabry's disease.
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