Methods for the treatment of senile dementia of the alzheimer's type
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Publication Number
US-9034923-B2
Publication Date
2015-05-19
Expiration Date
Abstract
The present invention relates to the treatment of Senile Dementia of the Alzheimer's Type (SDAT) by administering to the patient and effective amount of 1-alkyl, 2-acyl-glycerol. A specific 1-alkyl, 2-acyl-glycerol is shown below:
Core Innovation
The disclosure addresses senile dementia of the Alzheimer's Type (SDAT) through peripheral measurement of ethanolamine phospholipids in human serum, with emphasis on ethanolamine plasmalogens (EtnPls) and serum lipid ratios. It relates systemic depletion of ether lipids, including EtnPls, to peroxisomal dysfunction and to downstream SDAT-relevant pathology pathways, including membrane cholesterol and amyloid precursor protein (APP) processing.
Diagnostic and risk-assessment methods compare serum metabolite levels and ratios of ethanolamine phospholipid species in a subject to reference populations. The metabolite panels include diacyl, plasmanyl, and plasmenyl phosphatidylethanolamine (PtdEt) species, free DHA, and ratios such as EtnPls 16:0/22:6 (M19) relative to PtdEt 16:0/18:0 (M01), with differential diagnosis versus non-SDAT dementias and reported cohort findings related to age, dementia severity, and post-mortem amyloid pathology.
Therapeutic strategies are described to restore ether lipid and/or EtnPl levels using metabolic precursors within the ether lipid pathway and/or peroxisome-proliferator receptor (PPAR) agonists. The disclosure also includes mass spectrometry-based quantification and identification of specific biomarkers from serum metabolite panels, together with in vitro data in a plasmalogen-deficient cell model showing metabolic precursor restoration of EtnPl/DHA pools and effects on cholesterol.
Claims Coverage
Four independent claims are present across the items, all directed to treating senile dementia of the Alzheimer's Type (SDAT) by administering a therapeutically effective amount of a specified 1-alkyl, 2-acyl-glycerol, or a pharmaceutically acceptable salt. The inventive features center on SDAT treatment and on the lipid structure defined by sn-1 alkyl and sn-2 acyl side chains or by a formula-defined 1-alkyl, 2-acyl-glycerol.
Treating SDAT by administering defined 1-alkyl, 2-acyl-glycerol with specified sn-1 and sn-2 side chains
A method for the treatment of senile dementia of the Alzheimer's Type (SDAT) by administering to a patient a therapeutically effective amount of a 1-alkyl, 2-acyl-glycerol, or a pharmaceutically acceptable salt thereof, with sn-1 alkyl and sn-2 acyl side chains limited to the listed member sets.
Treating SDAT by administering a formula-defined 1-alkyl, 2-acyl-glycerol
A method for the treatment of senile dementia of the Alzheimer's Type (SDAT) by administering to a patient in need thereof a therapeutically effective amount of a 1-alkyl, 2-acyl-glycerol of the formula, or a pharmaceutically acceptable salt thereof.
The claim coverage centers on SDAT treatment by administration of a therapeutically effective amount of a 1-alkyl, 2-acyl-glycerol, or pharmaceutically acceptable salt. One independent claim additionally defines the sn-1 alkyl and sn-2 acyl options by explicit fatty-chain identities, while the other is directed to a formula-defined 1-alkyl, 2-acyl-glycerol.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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