The Cleveland Clinic Foundation

The Procter Gamble Company

Liposcience, Inc.

Children's Hospital Research Center at Oakland

Other

Frantz Biomarkers, LLC

Stanley Leon Hazen

Zeneng Wang

Renliang Zhang

Jonathan D Smith

Marc S Penn

Jose Carlos Garcia-Garcia

Bruce S Levison

George Franklin Gerberick

John August Wos

Michael Reilly

Xiaodong Gu

Lemin Zheng

Michael Kinter

James D Otvos

Dennis W Bennett

Elias J Jeyarajah

Justyna E Wolak-Dinsmore

Thomas M O'Connell

Steven P Matyus

David Blair Cody

David Thomas Stanton

Thomas Alfred Inglin

Angela Jane Deutsch

Claudia R Morris

Jodie Michele Reed

Jodie Michelle Reed

Mark Robert Sivik

Lori Ann Reinsalu

Satish C Kalhan

Suzy Comhair

Jonathan Mark Brown

Shuhui Wang Lorkowski

Vincent Peter Sica

Timothy R Baker

Lian Shan

Maryam Zamanian-Daryoush

Stephen James Nicholls

Xiandong Gu

Bruce L Levison

Joseph Didonato

Provided herein are compositions, systems, kits, and methods for performing an apoA1 exchange assay to determine the risk of MACE and/or for conducting an action based on the assay results. In some embodiments, methods are provided for generating, or receiving, a report that graphically displays: i) the subjects ApoA1 exchange rate in a sample as lower than a control or threshold value, and ii) the subjects risk of a major adverse cardiac event (MACE) and/or cardiovascular disease as being higher than normal.

ApoA1 exchange rate assays in serum

The present invention provides methods, kits, and compositions for: i) detecting the level of 3-bromotyrosine in a sample that has been treated to liberate 3-bromotyrosine from 4-O-glucuronide-3-bromotyrosine, and/or ii) detecting the level of 4-O-glucuronide-3-bromotyrosine, and/or the combined level of both 4-O-glucuronide-3-bromotyrosine and 3-bromotyrosine, in a sample that has not been treated to liberate 3-bromotyrosine from 4-O-glucuronide-3-bromotyrosine. In certain embodiments, such detected levels are used to: i) identify the presence, severity, or risk of an eosinophilic disorder (e.g., asthma or a TH2-high eosinophilic disorder); ii) identify therapy effective for treating asthma or an eosinophilic disorder; or iii) identify patients suitable for treatment with therapeutic agents targeted to asthma or an eosinophilic disorder.

Detection of glucuronidated and 3-bromotyrosine

Methods of characterizing a test subject's risk of having or developing cardiovascular disease are provided. The methods include using an analytic device to determine levels of choline-related trimethylamine-containing compounds such as trimethylamine N-oxide, choline, or betaine in a biological sample obtained from the subject and comparing the levels of the choline-related trimethylamine-containing compound in the subject's biological sample to a control value. The test subject's risk of having cardiovascular disease is then characterized as higher if the levels of the choline-related trimethylamine-containing compound are higher than the control value. Also provided are methods of identifying a subject at risk of experiencing a complication of atherosclerotic cardiovascular disease, and methods of evaluating the efficacy of a cardiovascular therapeutic agent in a subject with cardiovascular disease using levels of choline-related trimethylamine-containing compounds.

Trimethylamine compounds as risk predictors of cardiovascular disease

Provided herein are compositions, systems, and methods for treating a disease, such as kidney and/or cardiovascular disease, with an agent that reduces the production of trimethylamine (TMA) or trimethylamine-n-oxide (TMAO) in a subject. In certain embodiments, the agent is: i) 3,3-dimethyl-1-butanol (DMB) or a DMB derivative or related compound, ii) acetylsalicylic acid or derivative thereof (e.g., with an enteric coating for delivery to the colon and/or cecum); iii) a flavin monooxygenase 3 (FMO3) inhibitor; iv) a gut TMA lyase inhibitor; v) an antibiotic or antimicrobial; vi) a probiotic or prebiotic; vii) an antiplatelet agent; or viii) a TMA and/or TMAO sequestering agent.

Treating and preventing disease with TMA and TMAO lowering agents

The present invention provides markers and methods for determining whether a subject, particularly a human subject, has or is at risk of developing, a disease such as cardiovascular disease, diabetes mellitus, insulin resistance, metabolic syndrome, NAFLD (Nonalcoholic Fatty Liver Disease) or NASH (Nonalcoholic Steatohepatitis) (e.g., within the ensuing year, two years, and/or three years). The present application also relates to the use of such markers and methods for monitoring the status of such diseases in a subject or the effects of therapeutic agents on subjects with such diseases.

TMA-formation inhibitor treatment for elevated TMA-containing compound diseases

A defined peak region residing between about 3.2 and 3.4 ppm of a proton NMR spectrum of an in vitro biosample is electronically evaluated to determine a level of trimethylamine-N-oxide ('TMAO'). The biosamples may be any suitable biosamples including human serum with a normal biologic range of between about 1-50 &#x3bc;M or urine with a normal biologic range of between about 0-1000 &#x3bc;M.

NMR quantification of TMAO

Provided herein are compositions, systems, and methods for causing weight loss and treating and/or preventing a disease or condition, such as obesity, diabetes, and cancer, with an agent or procedure that inhibits the TMA/FMO3/TMAO pathway in a subject.

Treating disease and promoting weight loss by inhibiting the TMA/FMO3/TMAO pathway

A method of inhibiting the conversion of choline to trimethylamine (TMA) and lowering TMAO in an individual by providing a composition comprising (2-hydroxyethyl) dimethylsulfonium with a counterion wherein the counterion is selected from chloride, bromide or iodide.

Methods for inhibiting conversion of choline to trimethylamine (TMA)

The present invention to provides methods, kits, and compositions for: i) detecting the level of 3-bromotyrosine in a sample that has been treated to liberate 3-bromotyrosine from 4-O-glucuronide-3-bromotyrosine, and/or ii) detecting the level of 4-O-glucuronide-3-bromotyrosine, and/or the combined level of both 4-O-glucuronide-3-bromotyrosine and 3-bromotyrosine, in a sample that has not been treated to liberate 3-bromotyrosine from 4-O-glucuronide-3-bromotyrosine. In certain embodiments, such detected levels are used to: i) identify the presence, severity, or risk of an eosinophilic disorder (e.g., asthma or a TH2-high eosinophilic disorder); ii) identify therapy effective for treating asthma or an eosinophilic disorder; or iii) identify patients suitable for treatment with therapeutic agents targeted to asthma or an eosinophilic disorder.

A method of inhibiting the conversion of choline to trimethylamine (TMA) and lowering TMAO by providing a composition comprising a compound set forth in Formula (I): 

Trimethylamine-containing compounds for diagnosis and prediction of disease

A method of inhibiting the conversion of choline to trimethylamine (TMA) and lowering TMAO in an individual by providing a composition comprising a compound set forth in Formula (I): 

The invention provides a method of inhibiting the conversion of carnitine to trimethylamine (TMA) and lowering TMAO in an individual comprising administering to the individual one or more compositions comprising a compound set forth in Formula (I): Wherein the compound is administered in an amount effective to inhibit conversion of carnitine to TMA in the individual.

Methods for inhibiting conversion of carnitine to trimethylamine (TMA)

The invention provides one or more methods of inhibiting the conversion of choline to trimethylamine (TMA) and lowering TMAO in an individual comprising administering to the individual one or more compositions comprising a compound set forth in Formula (I): wherein the compound is administered in an amount effective to inhibit formation of trimethylamine (TMA) from choline in the individual.

Growing community of inventors

Pepper Pike, OH, United States of America

Stanley Leon Hazen