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Publication Number
US-8993623-B2
Publication Date
2015-03-31
Expiration Date
Abstract
The present invention relates to a 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 of Dihydroxyacetone phosphate (DHAP); 1-acyl-DHAP; 1-alkyl-DHAP; 1-alkyl-glyceraldehyde-3-phosphate (G3P); 1-alkyl, 2-acyl-G3P; 1-alkyl, 2-acyl-glycerol; 1-alkyl,2-acyl-glycerylphosphatidylethanolamine (GPE), 1-alkyl, diacyl glycerol (sn-1=16:0, sn-2=docosohexaenoic acid (DHA); sn-3=DHA) (sn-1 position has an alkyl ether bond, sn-2 and sn-3 positions have acyl bonds); 1-alkyl diacyl glycerol (sn-1=16:0, sn-2=18:1, sn-3=18:1) (sn-1 position has an alkyl ether bond, sn-2 and sn-3 positions have acyl bonds); triacyl glycerol (sn-1=16:0, sn-2=DHA, sn-3=DHA) (all three positions have acyl bonds); and triacyl glycerol (sn-1=16:0, sn-2=18:1, sn-3=18:1) (all three positions have acyl bonds) and pharmaceutically acceptable salts thereof.
Core Innovation
The invention relates to diagnosing and treating senile dementia of the Alzheimer’s type (SDAT) using serum ethanolamine phospholipid biomarkers, in particular ethanolamine plasmalogens. Specific ethanolamine plasmalogen species are decreased in SDAT across dementia severity and in subjects with confirmed amyloid pathology, and the decrease is associated with dementia severity and cognitive performance.
Reduced ethanolamine plasmalogen availability is linked to a proposed causal mechanism involving peroxisomal ether-lipid synthesis. The document discusses the DHAP synthase pathway and characterizes ethanolamine plasmalogen depletion as connected to membrane dysfunction and downstream amyloid processes, with the depletion observable systemically in serum.
The document describes methods to measure and quantify serum metabolites, including ethanolamine plasmalipid species, and to use metabolite levels and/or ratios/scores to diagnose SDAT versus non-SDAT and to identify individuals at risk. It also describes using such measures for stratification related to potential therapy responsiveness, including stratification for PPAR agonists such as rosiglitazone.
Claims Coverage
The partial content includes two independent claims directed to lowering cholesterol in a patient by administering a therapeutically effective amount of a defined 1-alkyl, 2-acyl-glycerol (or a pharmaceutically acceptable salt). The inventive features are directed to the defined side-chain selections at the sn-1 and sn-2 positions in the 1-alkyl, 2-acyl-glycerol.
Defined 1-alkyl,2-acyl-glycerol for lowering cholesterol
A method of lowering cholesterol in a patient in need thereof by administering to the patient a therapeutic effective amount of a 1-alkyl, 2-acyl-glycerol (or a pharmaceutically acceptable salt thereof) in which the alkyl side chain at the sn-1 position is selected from 16:0, 18:0, 18:1, 18:2, or 18:3, and the acyl side chain at the sn-2 position is selected from 18:1, 18:2, 18:3, 20:4, 20:5, 20:6, 22:4, 22:5, 22:6, 24:4, 24:5, or 24:6.
Broad 1-alkyl,2-acyl-glycerol administration for lowering cholesterol
A method of lowering cholesterol in a patient in need thereof by administering to the patient a therapeutically effective amount of a 1-alkyl, 2-acyl-glycerol of a stated formula (or a pharmaceutically acceptable salt thereof).
Across the included independent claims, cholesterol lowering is achieved by administering a therapeutically effective amount of a 1-alkyl, 2-acyl-glycerol (or pharmaceutically acceptable salt). One claim specifies the allowed sn-1 alkyl and sn-2 acyl fatty-chain options, while the other claim covers administration of a 1-alkyl, 2-acyl-glycerol defined by a formula.
Stated Advantages
Lowering cholesterol in a patient in need thereof.
Documented Applications
Lowering cholesterol in a patient in need thereof (via administration of a 1-alkyl, 2-acyl-glycerol or a pharmaceutically acceptable salt).
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