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Publication Number
US-10123989-B2
Publication Date
2018-11-13
Expiration Date
Abstract
The present invention relates to the method of lowering cholesterol in a patient in need thereof by administering to said patient a therapeutic effective amount of a compound selected from the group consisting of 1-alkyl, 2-acyl-glyceraldehyde-3-phosphate (G3P), 1-alkyl, 2-acyl glycerol and 1-alkyl, 2-acyl-glycerylphosphatidylethanolamine (GPE) or a pharmaceutically acceptable salt thereof.
Core Innovation
The invention relates to a dementia framework for Senile Dementia of the Alzheimer's Type (SDAT) and amyloid-b2 pathology, linking systemic depletion of ethanolamine plasmalogens and plasmanyl ethanolamine phospholipids to peroxisomal dysfunction. It associates changes in serum ether-lipid metabolites, including ethanolamine plasmalipids and plasmanyl ethanolamine phospholipids, with the dementia condition and amyloid-b2 related processes involving amyloid precursor protein (APP), b1-secretase, and b2-secretase.
The invention proposes diagnostic and risk assessment approaches based on measuring serum ethanolamine phospholipids, including EtnPls (ethanolamine plasmalipids), plasmanyl ethanolamine phospholipids, and PtdEt, with serum ratios used for diagnostic classification. It also proposes analytical measurement workflows using LC-MS/MS approaches including Q-Trap LC-MS/MS and related instrumentation configurations mentioned in the document.
For treatment concepts, the invention describes metabolic precursor and/or peroxisome-proliferator receptor activator (PPAR) agonist strategies, including mention of rosiglitazone (Avandia), connected to restoring or modifying ether-lipid and peroxisomal function-related lipid pools. In addition, it describes therapeutic intervention aimed at lowering cholesterol by administering ether-lipid pathway molecules, including 1-alkyl, 2-acyl-glyceraldehyde-3-phosphate (G3P), 1-alkyl, 2-acyl-glycerol, and 1-alkyl, 2-acyl-glycerylphosphatidylethanolamine (GPE) and related fatty-acid constituents.
Claims Coverage
The provided portion includes one independent claim covering a cholesterol-lowering method, with two dependent claims that narrow the selection of ether-lipid pathway compounds by compound type and by sn-1/sn-2 fatty-acid sidechain composition. The inventive features in the claim set focus on administering specific ether-lipid molecules or salts to a patient in need thereof.
Administering ether-lipid pathway molecules for cholesterol lowering
A method of lowering cholesterol in a patient in need thereof by administering a therapeutic effective amount of a compound selected from the group consisting of 1-alkyl, 2-acyl-glyceraldehyde-3-phosphate (G3P), 1-alkyl, 2-acyl-glycerol, and 1-alkyl, 2-acyl-glycerylphosphatidylethanolamine (GPE), or a pharmaceutically acceptable salt thereof.
Using a 1-alkyl, 2-acyl-glycerol compound
The method of lowering cholesterol where the administered compound is 1-alkyl, 2-acyl-glycerol.
Restricting sn-1/sn-2 fatty-acid sidechains of the administered compound
The method where the sidechains contain specified saturated or unsaturated fatty acids at the sn-1 and/or sn-2 positions, with allowed fatty-acid species enumerated for the sn-1 and sn-2 positions.
Across the claim set, cholesterol lowering is achieved by administering therapeutic effective amounts of specified ether-lipid pathway molecules (G3P, 1-alkyl, 2-acyl-glycerol, or GPE) or salts, with further narrowing to 1-alkyl, 2-acyl-glycerol and to compounds having enumerated sn-1 and/or sn-2 fatty-acid sidechain species.
Stated Advantages
Lowering cholesterol in a patient in need thereof.
Documented Applications
Cholesterol lowering by administering ether-lipid pathway molecules to a patient in need thereof.
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