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Ceramides and their use in diagnosing cvd

A technology of ceramides and alkyl chains, applied in disease diagnosis, markers used in chemical analysis, medical preparations containing active ingredients, etc., can solve problems such as interpretation of CRP

Active Publication Date: 2017-02-22
ZORA BIOSCIENCES OY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, none of the lipid-based markers listed (LDL-C, HDL-C, Lp(a), Lp-PLA2 (PLAC test)) provided clinically useful predictive information to assist physicians in classifying
In a research setting, CRP is promising, however it has been shown to be nonspecific (CRP is an acute phase reactant that can respond to many different stimuli, resulting in highly variable test results) and thus difficult to implement in the clinical setting. Interpretation of CRP values ​​in use
There remains an unmet need for diagnostic tests that can predict CV complications such as AMI (acute myocardial infarction), ACS (acute coronary syndrome), stroke and CV death

Method used

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  • Ceramides and their use in diagnosing cvd
  • Ceramides and their use in diagnosing cvd
  • Ceramides and their use in diagnosing cvd

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0247] study patients. The Corogene study was a prospective cohort study in which 5000 Finnish patients were sequentially sent to Helsinki University Central Hospital for diagnostic coronary angiography. In the present study, 436 CAD patients with >50% stenosis in at least one coronary artery were analyzed. In this nested-case-control study, each case was matched with a control subject. It was the case that CAD patients died from CV causes during a mean follow-up period of 2.5 years. Matched controls were CAD patients who did not die from any cause during the follow-up period. Matching criteria included: age, sex, body mass index, statin use, smoking, and type 2 diabetes.

[0248] Analytical method. For quantification, ceramides were extracted using a modified Folch lipid extraction method performed on a Hamilton Microlab Star robot as described in Jung HR et al., High throughput quantitative molecular lipidomics. Biochim Biophys Acta. 2011 Nov;1811(11):925-34 , which is ...

Embodiment 2

[0267] Model Comparison 1. In model comparison 1, a single ceramide substance (group A or B) was compared to a combination of two ceramides, one from group A and the other from group B. In model comparison 1, the fact that Pr(>Chi)<0.05 for the combined two marker models versus either single marker model indicates that the discriminative power of the combined model is significantly better than that of the single marker model, as shown in Table 4 below Show.

[0268] Table 4: Model Comparison 1

[0269]

Embodiment 3

[0271] Model Comparison 2. There is no specific reason to limit the discrimination model to combinations of only two ceramides. However, for practical purposes and for reasons of limiting costs, it is preferred to use as little ceramide as possible. Therefore, the benefits of increased sensitivity and specificity must be weighed against the additional expense of analyzing more molecular lipid species. In model comparison 2, a model using 2 ceramide substances is compared to a model using 3 ceramide substances, wherein the 3 ceramide markers include at least one group A ceramide and at least one group B ceramide . In model comparison 2, Pr(>Chi)<0.05 for the combined 3-marker model versus any of the two-marker models indicated that the discriminative ability of the three-marker model was significantly better than that of the two-marker model, as shown in Table 5 below Show.

[0272] Table 5: Model Comparison 2

[0273]

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Abstract

The present invention inter alia provides a method, and use thereof, of predicting CV complications such as AMI, ACS, stroke, and CV death by determining the concentrations of at least one ceramide of Group A and at least one ceramide of Group B in a biological sample and comparing those concentrations to a control. Finding a decreased concentration of at least one Group A ceramide and an increased concentration of at least one Group B ceramide indicates that the subject has an increased risk of developing one or more CV complications. Also provided area newly identified subset of ceramide molecules, labelled versions thereof, and kits and compositions comprising the same for use in predicting and / or diagnosing CV complications.

Description

[0001] Citations to related applications [0002] This application claims priority and benefit to U.S. Provisional Patent Application No. 62 / 012,543, filed June 16, 2014, and U.S. Patent Application No. 14 / 677,595, filed April 2, 2015, the entire contents of which are incorporated by reference Incorporated into this article. technical field [0003] This application relates generally to ceramide biomarkers and their use in identifying subjects at increased risk of developing cardiovascular (CV) complications such as AMI (acute myocardial infarction), ACS (acute coronary syndrome), stroke, or CV death application in the reader. Background technique [0004] Current CV markers, LDL-C, HDL-C and total cholesterol do not distinguish coronary artery disease (CAD) with high risk of CV complications such as AMI, ACS, stroke and CV death from patients with more stable disease patient or subject. [0005] The term myocardial infarction denotes pathologically the death of cardiomyo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/92
CPCG01N33/92G01N2800/32G01N2800/324A61K31/164C07B59/001G01N2405/08G01N2800/52G01N2800/50G01N2458/15
Inventor 雷约·拉克索宁
Owner ZORA BIOSCIENCES OY
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