Circulating bmp10 (bone morphogenic protein 10) in the assessment of atrial fibrillation

Patent metadata

Field	Value
Publication number	US-2021190801-A1
Application number	US-202117177673-A
Country	US
Kind code	A1
Filing date	Feb 17, 2021
Priority date	Aug 17, 2018
Publication date	Jun 24, 2021
Grant date	—

Abstract

The present invention relates to a method for assessing atrial fibrillation in a subject, said method comprising the steps of determining the amount of BMP 10 in a sample from the subject, and comparing the amount of BMP 10 to a reference amount, whereby atrial fibrillation is to be assessed. Moreover, the present invention relates to a method for diagnosing heart failure based on the determination of BMP 10 in a sample from a subject. Further, the present invention relates to a method for predicting the risk of a subject of hospitalization due to heart failure based on the determination of a BMP 10-type peptide in a sample from a subject.

First claim

1 . A method for assessing atrial fibrillation in a subject, comprising the steps of
a) determining, in at least one sample from the subject, the amount of a BMP 10-type peptide (Bone Morphogenic Protein 10-type peptide) and, optionally, the amount of at least one further biomarker selected from the group consisting of a natriuretic peptide, ESM-1 (Endocan), Ang2 (Angiopoietin 2) and FABP3 (Fatty Acid Binding Protein 3), and b) comparing the amount of the BMP 10-type peptide to a reference amount for the BMP 10-type peptide and, optionally, comparing the amount of the at least one further biomarker to a reference amount for said at least one further biomarker, whereby atrial fibrillation is to be assessed.

2 . The method of claim 1 , wherein the sample is selected from the group consisting of a blood, serum and plasma sample.

3 . The method of claim 1 , wherein the assessment of atrial fibrillation is the diagnosis of atrial fibrillation.

4 . The method of claim 3 , wherein an amount of the BMP 10-type peptide and, optionally, an amount of the at least one further biomarker above the reference amount is indicative for a subject suffering from atrial fibrillation and/or wherein an amount of the BMP 10-type peptide and, optionally, an amount of the at least one further biomarker below the reference amount is indicative for a subject not suffering from atrial fibrillation.

5 . The method of claim 1 , wherein the subject is suffering from atrial fibrillation, and wherein the assessment of atrial fibrillation is the differentiation between paroxysmal and persistent atrial fibrillation.

6 . The method of claim 5 , wherein an amount of the BMP 10-type peptide and, optionally, an amount of the at least one further biomarker above the reference amount is indicative for a subject suffering from persistent atrial fibrillation and/or wherein an amount of the BMP 10-type peptide and, optionally, an amount of the at least one further biomarker below the reference amount is indicative for a subject suffering from paroxysmal atrial fibrillation.

7 . The method of claim 1 , wherein the assessment of atrial fibrillation is the prediction of the risk of an adverse event associated with atrial fibrillation.

8 . The method of claim 7 , wherein an amount of the BMP 10-type peptide and, optionally, an amount of the at least one further biomarker above the reference amount is indicative for a subject who is at risk of suffering from an adverse event associated with atrial fibrillation and/or wherein an amount of the BMP 10-type peptide and, optionally, an amount of the at least one further biomarker below the reference amount is indicative for a subject who is not at risk of suffering from an adverse event associated with atrial fibrillation.

9 . The method of claim 1 , wherein the assessment of atrial fibrillation is the assessment of a therapy for atrial fibrillation.

10 . A method of aiding in the assessment of atrial fibrillation, said method comprising the steps of:
a) providing at least one sample from a subject, b) determining, in the at least one sample provided in step a), the amount of a BMP 10-type peptide (Bone Morphogenic Protein 10-type peptide) and, optionally, the amount of at least one further biomarker selected from the group consisting of a natriuretic peptide, ESM-1 (Endocan), Ang2 and FABP3 (Fatty Acid Binding Protein 3), and c) providing information on the determined amount of the BMP 10-type peptide and optionally on the determined amount of the at least one further biomarker to a physician, thereby aiding in the assessment of atrial fibrillation.

11 . A method for aiding in the assessment of atrial fibrillation, comprising:
a) providing an assay for a BMP 10-type peptide and, optionally, at least one further assay for a further biomarker selected from the group consisting of a natriuretic peptide, ESM-1 (Endocan), Ang2 and FABP3 (Fatty Acid Binding Protein 3), and b) providing instructions for using of the assay results obtained or obtainable by said assay(s) in the assessment of atrial fibrillation.

12 . A computer-implemented method for assessing atrial fibrillation, comprising
a) receiving, at a processing unit, a value for the amount of a BMP 10-type peptide, and, optionally at least one further value for the amount of at least one further biomarker selected from the group consisting of a natriuretic peptide, ESM-1 (Endocan), Ang2 and FABP3 (Fatty Acid Binding Protein 3), wherein said amount of the BMP 10-type peptide and, optionally, the amount of the at least one further biomarker have been determined in a sample from a subject, b) comparing, by said processing unit, the value or values received in step (a) to a reference or to references, and c) assessing atrial fibrillation based in the comparison step b).

13 . A method for diagnosing heart failure, said method comprising the steps of
(a) determining, in at least one sample from the subject, the amount of a BMP 10-type peptide (Bone Morphogenic Protein 10-type peptide) and, optionally, the amount of at least one further biomarker selected from the group consisting of a natriuretic peptide, ESM-1 (Endocan), Ang2, and FABP3 (Fatty Acid Binding Protein 3), and (b) comparing the amount of the BMP 10-type peptide to a reference amount for the BMP 10-type peptide and, optionally, comparing the amount of the at least one further biomarker to a reference amount for said at least one further biomarker, whereby heart failure is to be diagnosed.

14 . A method for predicting the risk of a subject of hospitalization due to heart failure, said method comprising the steps of
(a) determining, in at least one sample from the subject, the amount of a BMP 10-type peptide (Bone Morphogenic Protein 10-type peptide), and, optionally, the amount of at least one further biomarker selected from the group consisting of a natriuretic peptide, ESM-1 (Endocan), Ang2 and FABP3 (Fatty Acid Binding Protein 3), (b) comparing the amount of the BMP 10-type peptide to a reference amount, and optionally, comparing the amount of the at least one further biomarker to a reference amount for said at least one further biomarker, and (c) predicting the risk of a subject of hospitalization due to heart failure.

15 . A kit comprising an agent which specifically binds to a BMP 10-type peptide and at least one further agent selected from the group consisting of an agent which specifically binds to a natriuretic peptide, an agent which specifically binds to ESM-1, an agent which specifically binds Ang2 and an agent which specifically binds to FABP3.

16 . In vitro use of
(a) a BMP 10-type peptide, and/or (b) at least one agent that specifically binds to a BMP 10-type peptide, for predicting the risk of a subject of hospitalization due to heart failure.

17 . In vitro use of
i) a BMP 10-type peptide and optionally of at least one further bio marker selected from the group consisting of a natriuretic peptide, ESM-1 (Endocan), Ang2 and FABP3 (Fatty Acid Binding Protein 3), and/or ii) at least one agent that specifically binds to a BMP 10-type peptide, and, optionally, at least one further agent selected from the group consisting of an agent which specifically binds to a natriuretic peptide, an agent which specifically binds to ESM-1, an agent which specifically binds to Ang2 and an agent which specifically binds to FABP3, for assessing atrial fibrillation or for diagnosing heart failure.

18 . In vitro use of claim 16 , wherein the agent is an antibody, or an antigen-binding fragment thereof.

19 . In

Assignees

• Roche Diagnostics Operations Inc
• Univ Maastricht
• Acad Ziekenhuis Maastrict

Inventors

• Karl Johann
• Kastner Peter
• Wienhues-Thelen Ursula-Henrike
• Dietrich Manuel
• Ziegler Andre
• Schotten Ulrich

Classifications

• G01N33/6893 Primary

  related to diseases not provided for elsewhere · CPC title

• C07K16/22

  against growth factors {; against growth regulators} · CPC title

• G01N2800/325

  Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure · CPC title

• G01N2800/326

  Arrhythmias, e.g. ventricular fibrillation, tachycardia, atrioventricular block, torsade de pointes · CPC title

• C07K14/51

  Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor · CPC title