Methods for the diagnosis and risk assessment of plasmalogen deficiency mediated diseases of aging
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Publication Number
US-10302624-B2
Publication Date
2019-05-28
Expiration Date
Abstract
The present invention relates to methods for the diagnosis and risk assessment of plasmalogen deficiency mediated diseases of aging. The present invention describes the relationship between plasmalogen biosynthesis dysfunction and the biochemical and clinical manifestations of age related disorders. Specifically the present invention describes an increased prevalence of colon cancer, prostate cancer, lung cancer, breast cancer, ovary cancer, kidney cancer, cognitive impairment and dementia in subjects suffering from adult onset plasmalogen biosynthesis disorder (AO-PBD).
Core Innovation
The patent addresses adults older than forty years of age who have adult onset plasmalogen biosynthesis disorder characterized by decreased circulating plasmalogens. It states that adults with decreased circulating plasmalogens show increased prevalence of multiple age-related diseases, including colon, prostate, lung, breast, ovarian, and kidney cancers, and cognitive impairment or dementia. Measuring ether lipid plasmalogen species in serum is used to detect or monitor the disorder and to support a diagnostic or risk-assessment approach.
The patent describes generating quantifying data for one or more metabolite markers selected from plasmanyl glycerylphosphoethanolamines by mass spectrometry on one or more blood samples. It states that a result is generated comprising at least the presence of a decrease in the level of the one or more metabolite markers based on comparison of quantifying data to corresponding data obtained from one or more reference samples, and that the subject is assigned as having adult onset plasmalogen biosynthesis disorder based on the decrease. It additionally describes the use of an endogenous internal control metabolite to improve stability and reproducibility of the assessment.
The patent provides rationale that decreased plasmalogens associated with cancer and dementia are not driven by increased oxidative stress, because both plasmanyl and plasmenyl species decrease together. It also states that the approach distinguishes adult onset plasmalogen biosynthesis disorder-related pathology from Alzheimer’s disease pathology using comparison groups and includes epidemiological cutoffs based on observed decreases. The document further describes MS-based analytical platforms and workflows for obtaining the quantifying data, including multiple metabolite panels and comparison to normal or adult onset plasmalogen biosynthesis disorder reference groups.
Claims Coverage
The partial content includes two independent claims. Each independent claim centers on detecting or monitoring adult onset plasmalogen biosynthesis disorder in subjects older than forty years using mass spectrometry measurement of plasmanyl glycerylphosphoethanolamines, assigning the disorder based on decreased marker levels versus reference samples, and administering an age-related plasmalogen deficiency-targeted therapy.
Mass spectrometry-based detection, monitoring, and assignment using decreases in plasmanyl glycerylphosphoethanolamines
A method to detect or monitor adult onset plasmalogen biosynthesis disorder in a living subject older than forty years of age, comprising performing a mass spectrometry assay on at least one blood sample using specified mass spectrometers to obtain quantifying data for one or more metabolite markers selected from plasmanyl glycerylphosphoethanolamines, generating a result comprising at least the presence of a decrease in the level of said metabolite marker based on comparison to one or more reference samples, and assigning the subject as having adult onset plasmalogen biosynthesis disorder based on the decrease.
Mass spectrometry measurement of ionization products for plasmanyl glycerylphosphoethanolamines
A method to detect or monitor adult onset plasmalogen biosynthesis disorder in a living subject older than forty years of age, comprising introducing a blood sample into specified mass spectrometers to ionize one or more metabolite markers selected from plasmanyl glycerylphosphoethanolamines and form ionization products, measuring the amount of the ionization products to obtain quantifying data for said metabolite markers, identifying presence of a decrease in the level of the metabolite marker based on comparison to quantifying data from one or more reference samples, and assigning the subject as having adult onset plasmalogen biosynthesis disorder based on the decrease.
Both independent claims require mass spectrometry measurement of plasmanyl glycerylphosphoethanolamines in blood samples, comparison to reference samples to identify decreased metabolite marker levels, and assignment of adult onset plasmalogen biosynthesis disorder.
Stated Advantages
Improves stability and reproducibility of the assessment by using an endogenous internal control metabolite.
Documented Applications
Detecting or monitoring adult onset plasmalogen biosynthesis disorder in a living subject older than forty years of age using mass spectrometry measurement of plasmanyl glycerylphosphoethanolamines and assigning the subject based on decreased marker levels versus reference samples.
Assessing increased prevalence of multiple age-related diseases, including colon, prostate, lung, breast, ovarian, and kidney cancers, and cognitive impairment or dementia, in adults with decreased circulating plasmalogens via serum ether lipid plasmalogen species measurements and comparisons to reference groups.
Distinguishing adult onset plasmalogen biosynthesis disorder-related pathology from Alzheimer’s disease pathology using comparison groups as described in the document.
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