Molecule biomarkers of autism
Inventors
Cezar, Gabriela Gebrin • Smith, Alan M.
Assignees
Wisconsin Alumni Research Foundation • Stemina Biomarker Discovery Inc
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Publication Number
US-9547013-B2
Publication Date
2017-01-17
Expiration Date
Abstract
This invention provides methods and biomarkers for diagnosing autism by identifying cellular metabolites differentially produced in autistic patient samples versus non-autistic controls. Methods for identifying a unique profile of metabolites present of secreted in brain tissue, cerebrospinal fluid, plasma, or biofluids of autistic samples are described herein. The individual metabolites or a pattern of secreted metabolites provide metabolic signatures of autism, which can be used to provide a diagnosis thereof.
Core Innovation
The invention relates to detecting levels of cellular metabolites in an individual suspected of having autism by assaying a biosample comprising brain tissue. The method detects levels of a plurality of cellular metabolites selected from N-acetylaspartylglutamic acid, 2-aminooctanoic acid, 5-hydroxylysine, vinylacetylglycine, proline, betaine, 3-carboxy-1-hydroxypropylthiamine diphosphate, 3′-sialyllactosamine, 3,4-dihydroxybenzylamine, dipalmitoyl-phosphatidylcholine, and SAICAR.
The detection is performed using liquid chromatography electro spray-ionization time of flight mass spectrometry to determine a metabolic biochemical fingerprint from autistic versus non-autistic samples. The metabolite range includes small metabolites having a molecular weight of about 10 Daltons to about 1500 Daltons, and the metabolite set and corresponding altered metabolite features support distinguishing autism-associated metabolic differences.
The document further describes autism diagnostic metabolomics based on metabolites that are differentially secreted or produced in autistic versus non-autistic samples, and reports that pathway associations can include glutamate, cysteine/methionine, tryptophan, and GABA metabolism. In addition to brain tissue, the document refers to biofluids such as cerebrospinal fluid and plasma as translational contexts for the described metabolite-based diagnosis.
Claims Coverage
The independent claims cover methods for detecting levels of a plurality of cellular metabolites in autism-relevant biosamples using liquid chromatography electro spray-ionization time of flight mass spectrometry. Across the two independent claims, the inventive coverage includes assay criteria for brain tissue, a defined plurality of metabolites, a specified molecular weight range, and the analytical detection modality.
Autism-suspected brain tissue metabolite detection by LC-ESI-TOF-MS
A method of detecting levels of cellular metabolites in an individual suspected of having autism, comprising obtaining a biosample comprising brain tissue, and detecting levels of a plurality of cellular metabolites in the biosample using liquid chromatography electro spray-ionization time of flight mass spectrometry, wherein the cellular metabolites are selected from N-acetylaspartylglutamic acid, 2-aminooctanoic acid, 5-hydroxylysine, vinylacetylglycine, proline, betaine, 3-carboxy-1-hydroxypropylthiamine diphosphate, 3′-sialyllactosamine, 3,4-dihydroxybenzylamine, dipalmitoyl-phosphatidylcholine, and SAICAR.
Brain tissue metabolite assay with 10–1500 Da range by LC-ESI-TOF-MS
A method of detecting levels of a plurality of cellular metabolites in a biosample comprising assaying a biosample comprising brain tissue isolated from a human patient suspected of having autism for levels of a plurality of cellular metabolites having a molecular weight of from about 10 Daltons to about 1500 Daltons, and detecting levels of the plurality of cellular metabolites in the biosample by liquid chromatography electro spray-ionization time of flight mass spectrometry, wherein the plurality of cellular metabolites comprises N-acetylaspartylglutamic acid, 2-aminooctanoic acid, 5-hydroxylysine, vinylacetylglycine, proline, betaine, 3-carboxy-1-hydroxypropylthiamine diphosphate, 3′-sialyllactosamine, 3,4-dihydroxybenzylamine, dipalmitoyl-phosphatidylcholine, and SAICAR.
Together, the independent claims define detecting levels of a specified plurality of cellular metabolites in autism-suspected brain tissue biosamples using liquid chromatography electro spray-ionization time of flight mass spectrometry, with one claim additionally requiring a molecular weight range of about 10 Daltons to about 1500 Daltons.
Stated Advantages
Provides a non-invasive translational context for metabolite-based autism diagnosis using biofluids such as cerebrospinal fluid and plasma, compared to tissue biopsy.
Documented Applications
Autism diagnostic metabolomics using metabolite biomarkers differentially secreted or produced in autistic versus non-autistic samples, using brain tissue biosamples and, as a translational context, biofluids such as cerebrospinal fluid and plasma.
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