Biomarkers of autism spectrum disorder
Inventors
West, Paul • Burrier, Robert E. • Egnash, Laura • Smith, Alan • Bais, Preeti
Assignees
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Publication Number
US-11268966-B2
Publication Date
2022-03-08
Expiration Date
Abstract
Methods for identifying metabolic signatures in blood plasma which are unique to autism are described herein. Samples are analyzed using multiple chromatographic-mass spectrometry-based techniques to orthogonally measure a broad range of small molecular weight metabolites differentially produced in autistic patient samples versus non-autistic control samples. These individual metabolites or a panel of such metabolites serve as metabolic signatures of autism. Such metabolic signatures are used in diagnostic methods to accurately identify individuals with autism spectrum disorder (ASD).
Core Innovation
The invention relates to autism-specific metabolomic biomarker discovery by assaying a biosample obtained from a human subject for a plurality of small molecule metabolites by mass spectrometry and quantifying an amount of each metabolite. The measured amounts are compared to corresponding amounts in non-autistic control biosamples, and statistically significant differences are determined for the specified metabolite panel.
The method specifies a plurality of small molecule metabolites associated with autism spectrum disorder, including 2-aminooctanoic acid, acesulfame, asymmetric dimethylarginine (ADMA), 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF), choline, cysteine, cystine, dehydroepiandrosterone sulfate (DHEAS), glycine, glycocholic acid, hypoxanthine, indoleacrylic acid, indoxyl sulfate, specified LysoPC/LysoPE species, methionine, p-cresol sulfate, phenylalanine, phenyllactic acid, proline, serotonin, tryptophan, uric acid, and valine.
A further aspect of the invention applies the assay to a human subject less than two years of age. In this early-age context, the metabolite panel comprises CMPF and at least one metabolite selected from a specified list, and statistically significant differences are determined versus non-autistic control biosamples.
Claims Coverage
The provided claim set includes two independent claims. Each independent claim centers on assaying a human biosample for a specified plurality of small molecule metabolites by mass spectrometry, quantifying each metabolite, and determining statistically significant differences relative to non-autistic control biosamples, with one independent claim further limited to subjects less than two years of age and a narrowed metabolite panel requirement.
Autism metabolite panel by mass spectrometry with statistical comparison to non-autistic controls
Assaying a biosample obtained from a human subject for a plurality of small molecule metabolites by mass spectrometry; quantifying an amount of each small molecule metabolite; and determining whether the amount of each small molecule metabolite displays a statistically significant difference compared to an amount of each small molecule metabolite in non-autistic control biosamples, wherein the plurality of small molecule metabolites comprises the specified set including 2-aminooctanoic acid, acesulfame, asymmetric dimethylarginine (ADMA), CMPF, choline, cysteine, cystine, DHEAS, glycine, glycocholic acid, hypoxanthine, indoleacrylic acid, indoxyl sulfate, specified LysoPC/LysoPE species, methionine, p-cresol sulfate, phenylalanine, phenyllactic acid, proline, serotonin, tryptophan, uric acid, and valine.
Early-age autism metabolite panel with CMPF requirement and statistical comparison to non-autistic controls
Assaying a biosample obtained from a human subject that is less than two years of age for a plurality of small molecule metabolites by mass spectrometry; quantifying an amount of each small molecule metabolite; and determining whether the amount of each small molecule metabolite displays a statistically significant difference compared to an amount of each small molecule metabolite in non-autistic control biosamples, wherein the plurality of small molecule metabolites comprises CMPF and at least one metabolite selected from the specified list including 2-aminooctanoic acid, acesulfame, ADMA, choline, cysteine, cystine, DHEAS, glycine, glycocholic acid, hypoxanthine, indoleacrylic acid, indoxyl sulfate, specified LysoPC/LysoPE species, methionine, p-cresol sulfate, phenylalanine, phenyllactic acid, proline, serotonin, tryptophan, uric acid, and valine.
Across both independent claims, the core claim coverage is directed to mass-spectrometry quantification of a defined metabolite panel and statistical determination of differences versus non-autistic control biosamples. One claim covers a broader fixed metabolite plurality, while the other restricts use to subjects less than two years of age and requires inclusion of CMPF with at least one additional metabolite from the specified list.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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