Method of diagnosing and treating asphyxia
Inventors
Keller, Matthias • Deigner, Hans-Peter • Enot, David • Kohl, Matthias • Solberg, Ronnaug • Saugstad, Olga • Koal, Therese
Assignees
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Publication Number
US-11313866-B2
Publication Date
2022-04-26
Expiration Date
Abstract
A method for in vitro diagnosing asphyxia and disorders related thereto, a method of in vitro estimating duration of hypoxia in a patient subjected to asphyxia, and a method for in vitro monitoring of normoxic, hypoxic and hyperoxic conditions and/or normobaric and hyperbaric oxygen therapy, includes quantitatively detecting in a biological sample of a patient a plurality of asphyxia specific endogenous compounds which are selected from the group consisting of biogenic amines; carnitine-derived compounds; amino acids; bile acids; carboxylic acids; eicosanoids; lipids; precursors of cholesterol, cholesterol metabolites; prostanoids; and sugars.
Core Innovation
The invention provides an in vitro early diagnosing and treating method for asphyxia and disorders related thereto in a neonate. The method selects at least three asphyxia specific compounds and quantitatively detects the selected compounds in the blood of a neonate by measuring concentration, level, or amount for each compound. The detecting and measuring are used to generate values for calibration and diagnosis.
The method calibrates the measured values by comparing the values to asphyxia-positive or asphyxia-negative reference levels of the at least three selected asphyxia specific compounds. Based on the comparing, the method positively diagnoses asphyxia or an asphyxia disorder and the duration of the asphyxia in the neonate. The diagnosis is used as a basis for administering treatment to the diagnosed neonate.
The method includes selecting specific asphyxia specific compounds, including 22-R-Hydroxycholesterol, 24-S-Hydroxycholesterol, 25-Hydroxycholesterol, 27-Hydroxycholesterol, 20α-Hydroxycholesterol, 22S-Hydroxycholesterol, 24,25-Epoxycholesterol, 3β,5α,6β-Trihydroxycholestan, 7α-Hydroxycholesterol, 7-Ketocholesterol, 5β,6β-Epoxycholesterol, 4β-Hydroxycholesterol, Desmosterol, 7-Dehydrocholesterol, Cholestenone, Lanosterol, and 24-Dihydrolanosterol. The method also optionally constrains the selected compounds to have molecular weight of less than 1500 Dalton.
Claims Coverage
Two independent claims are present, each covering an in vitro early diagnosing and treating approach for neonatal asphyxia using quantitative measurement of at least three asphyxia specific compounds, calibration against asphyxia-positive or asphyxia-negative reference levels, and positive diagnosis to guide administration of treatment. One independent claim further specifies an expanded set of analytes, while both allow detection modalities and calibration via comparing.
In vitro early diagnosing and treating of neonatal asphyxia using at least three quantified asphyxia specific compounds calibrated to reference levels
A method for in vitro early diagnosing and treating asphyxia and disorders related thereto by selecting at least three asphyxia specific compounds; quantitatively detecting the compounds in the blood of a neonate by measuring concentration, level, or amount; calibrating by comparing the measured values to asphyxia-positive or asphyxia-negative reference levels; based on the comparing, positively diagnosing asphyxia or an asphyxia disorder or its duration; and administering a treatment selected from administering oxygen, administering hypothermia, and administering a compound that targets an enzyme involved in the synthesis of an asphyxia specific metabolite, wherein the at least three asphyxia specific compounds are selected from a listed group of specific hydroxysterols and related sterols.
In vitro early diagnosing and treating using an analyte set of at least three quantified asphyxia specific compounds with neonatal blood calibration and duration diagnosis
A method for in vitro early diagnosing and treating asphyxia and disorders related thereto by selecting at least three asphyxia specific compounds; quantitatively detecting the compounds in the blood of a neonate by measuring concentration, level, or amount; calibrating by comparing the measured values to asphyxia-positive or asphyxia-negative reference levels; based on the comparing, positively diagnosing asphyxia or an asphyxia disorder and its duration in the neonate; and administering a treatment selected from administering oxygen, administering hypothermia, and administering a compound that targets an enzyme involved in the synthesis of an asphyxia specific metabolite, wherein the at least three asphyxia specific compounds comprise at least three analytes selected from a large group of named metabolites and lipid-related analytes.
Both independent claims center on selecting at least three asphyxia specific compounds, quantifying them in neonatal blood, calibrating by comparison to asphyxia-positive or asphyxia-negative reference levels, and positively diagnosing asphyxia, including duration, followed by administering oxygen, hypothermia, or an enzyme-targeting compound. One independent claim specifies a particular sterol-focused compound list, and the other specifies a broader multi-analyte list.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Diagnosing and treating asphyxia and disorders related thereto in a neonate using in vitro early diagnosis.
Diagnosing asphyxia disorder duration in the neonate based on calibrated quantitative measurements.
Diagnosing and treating hypoxic ischemic encephalopathy in the context of asphyxia-related disorders.
Use in disorders related to asphyxia including perinatal asphyxia, choking, drowning, electric shock, injury, or inhalation of toxic gases, where the related disorder is hypoxic ischemic encephalopathy.
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