Marker for acid sphingomyelinase disorders and uses thereof
AssigneeGenzyme Corporation
InventorsWei-Lien Chuang, Gerald F. Cox, X. Kate Zhang
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Abstract
The present disclosure provides methods of screening, diagnosing, monitoring and/or treating acid sphingomyelinase (ASM) disorders such as Niemann-Pick disease. In particular, the methods encompass techniques for improved diagnosis and/or treatment of an ASM disorder, for example using enzyme replacement therapy.
Claims19
A method of monitoring adverse side effects of acid sphingomyelinase (ASM) deficiency treatment in a human subject, wherein the method comprises:
- administering to the subject a starting dose of recombinant human acid sphingomyelinase (rhASM) or a modified rhASM,
- collecting a biological sample from the subject three or more days after the administration of a first dose of rhASM or modified rhASM,
- measuring a level of lyso-sphingomyelin (lyso-SPM) in the sample,
- comparing the level of lyso-SPM in the sample to a reference level, and
- detecting an adverse side effect if the level of lyso-SPM in the sample is greater than the reference level, and wherein the adverse side effects comprise production of toxic levels of metabolites.
A method of calibrating a dosage of a recombinant human acid sphingomyelinase (rhASM) or modified rhASM for treating an acid sphingomyelinase (ASM) deficiency in a subject, comprising
- collecting a biological sample from the subject after administration of a first dose of the rhASM or modified rhASM having a first concentration,
- measuring a level of lyso-sphingomyelin (lyso-SPM) in the biological sample, and
- comparing the level of lyso-SPM in the sample to a reference level,
- wherein the dosage of the rhASM or modified rhASM can be increased if the level of lyso-SPM in the biological sample is less than or equal to the reference level, or less than 1.1-10 fold greater than a reference level, and can be reduced if greater than the reference level, or if at least 1.1-10 fold greater the reference level.
A method of determining an effective dose of a recombinant human acid sphingomyelinase (rhASM) or modified rhASM for treating an acid sphingomyelinase (ASM) deficiency in a human subject, comprising
- collecting a biological sample from the subject three or more days after administration of a first dose of the rhASM or modified rhASM for treating the ASMD,
- measuring a level of lyso-sphingomyelin (lyso-SPM) in the biological sample, and
- comparing the level of lyso-SPM in the sample to a reference level, wherein a decrease of the level of lyso-SPM compared to a reference level indicates efficacy of the rhASM or modified rhASM dose.
Dependencies are inferred from the claim text.