The Cleveland Clinic Foundation

Other

Zeneng Wang

Stanley Leon Hazen

Bruce S Levison

Bruce L Levison

Stanley L Hanzen

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

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

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.

Trimethylamine-containing compounds for diagnosis and prediction of disease

Provided herein are compositions for the treatment and/or prevention of cardiovascular disease (CVD), and methods of application and use thereof. In particular, the present invention provides treatment and/or prevention of cardiovascular disease with compounds that inhibit the production of TMA in the gut, such as 3,3-dimethyl-1-butanol (DMB) or other compounds represented by Formula I or as shown in FIGS.-

Treatment and prevention of cardiovascular disease and thrombosis

Provided herein are compositions for the treatment and/or prevention of cardiovascular disease (CVD), and methods of application and use thereof. In particular, the present invention provides treatment and/or prevention of cardiovascular disease with 3,3-dimethyl-1-butanol (DMB) and related compounds, and pharmaceutical formulations thereof. In other embodiments, the present invention provides methods of administering a gut flora targeting antibiotic to a subject prior to a procedure that is associated with a risk of causing thrombosis, heart-attack, and/or platelet hyper-responsiveness.

Treatment of cardiovascular disease and thrombosis

Methods for characterizing a test subject's, particularly a human test subject's, risk of having cardiovascular disease or developing cardiovascular disease are provided. Also provided are methods for characterizing a test subject's risk of experiencing a complication of cardiovascular disease near term. The methods comprise determining levels of one or more carbamylated biomarkers in a bodily fluid of the test subject and/or comparing these levels with a reference value. In certain embodiments, the carbamylated biomarkers are carbamylated albumin, carbamylated fibrinogen, carbamylated immunoglobulin and carbamylated apolipoprotein A. In other embodiments, particularly where the test subject does not have clinical evidence of renal disease, the carbamylated biomarker is free and/or total peptide-bound homocitrulline.

Carbamylated proteins and risk of cardiovascular disease

A diagnostic method of monitoring anti-inflammatory and/or antioxidant actions of therapeutic agents comprises determining the level of at least one systemic marker indicative of inflammation or oxidation in a bodily sample taken from a subject at base line or following administration of the therapeutic agent. The marker includes at least one of MPO activity, MPO mass, select MPO-generated oxidation products, and combinations thereof. The level of the systemic marker is compared with a predetermined value to monitor the anti-inflammatory and/or antioxidant actions of the therapeutic agent.

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Shaker Heights, OH, United States of America

Zeneng Wang