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US 10,591,478 B2Granted
Methods for molecular classification of fatty liver by high-throughput protein post-translational modifications
AssigneeRoseman University of Health Sciences
InventorsThuc T. Le, Yasuyo Urasaki, Ronald R. Fiscus
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Abstract
The present invention is directed towards methods for treating non-alcoholic fatty liver disease (NAFLD) in a patient and determining prognosis of NAFLD in a patient.
Claims42
A method of determining a sub-classification of non-alcoholic fatty liver disease (NAFLD) comprising:
- measuring the activity of a metabolic and/or signaling pathway protein in liver tissue obtained from a subject, wherein the activity is measured using a capillary isoelectric focusing (cIEF) immunoassay, wherein the activity is defined by a post-translational modification chosen from methylation, glycosylation, and phosphorylation;
- detecting changes in isoelectric point (pI) of the metabolic and/or signaling pathway protein;
- quantifying the post-translational modification of the metabolic and/or signaling pathway protein by comparing the pI of the metabolic and/or signaling pathway protein with a normal pI for the metabolic and/or signaling pathway protein;
- creating a post-translational modification profile for the metabolic and/or signaling pathway protein;
- and
- identifying an abnormal post-translationally modified protein, wherein a change in pI of 10% or more from the normal pI indicates the presence of an abnormal post-translational modification.
3 more elements
A method of treating non-alcoholic fatty liver disease (NAFLD) in a patient comprising:
- obtaining a capillary isoelectric focusing (cIEF) profile using a cIEF immunoassay of a sample obtained from the patient, wherein the cIEF profile includes isoelectric point (pI) information for one or more proteins, wherein the one or more proteins are components of a metabolic and/or signaling pathway related to an NAFLD pathology;
- comparing the pI of the one or more proteins with a normal pI for the one or more proteins;
- identifying a protein with an isoelectric point that deviates from the normal pI, wherein a change in pI of 10% or more from the normal pI indicates the presence of an abnormal post-translational modification;
- and
- selecting and administering an effective amount of a therapeutic agent selected from agents that target a metabolic and/or signaling pathway identified as being abnormal.
2 more elements
A method for determining the prognosis of non-alcoholic fatty liver disease (NAFLD) in a patient comprising:
- measuring the activity of a metabolic and/or signaling pathway protein in liver tissue obtained from the patient, wherein the activity is measured using a capillary isoelectric focusing (cIEF) immunoassay, wherein the activity is a post-translational modification chosen from acetylation, glycosylation, and phosphorylation;
- detecting changes in isoelectric point (pI) of the metabolic and/or signaling pathway protein;
- quantifying the post-translational modification of the metabolic and/or signaling pathway protein by comparing the pI of the metabolic and/or signaling pathway protein with a normal pI for the metabolic and/or signaling pathway protein;
- creating a post-translational modification profile for the metabolic and/or signaling pathway protein;
- and
- comparing the post-translational modification profile of the patient with a post-translational modification profile of a patient with NAFLD and known disease progression and determining the prognosis based on the closest profile match.
3 more elements
Dependencies are inferred from the claim text.