In vitro method for identifying thoracic aortic aneurysms (TAA) in a subject

Patent metadata

Field	Value
Publication number	US-10907135-B2
Application number	US-201616083165-A
Country	US
Kind code	B2
Filing date	Dec 30, 2016
Priority date	Mar 7, 2016
Publication date	Feb 2, 2021
Grant date	Feb 2, 2021

Abstract

The present invention refers to an In vitro method for screening for subjects at risk of developing thoracic aortic aneurysm (TAA) or a disease causing TAA comprising: (a) measuring the expression pattern or level of at least A Disintegrin And Metalloproteinase with Thrombospondin Motifs 1 (ADAMTS1) obtained from an isolated biological sample of the subjects to be screened; and (b) comparing said expression pattern or level of at least ADAMTS1 of the subjects to be screened with an already established expression pattern or level, wherein reduced expression of at least ADAMTS1 is indicative of a thoracic aortic aneurysm (TAA).

First claim

The invention claimed is:

1. A method for the therapeutic treatment of a thoracic aortic aneurysm (TAA) in a patient, comprising administering a composition comprising an iNOS inhibitor to the patient, wherein the patient has increased accumulation of proteoglycans relative to a patient without TAA;
wherein the patient is suffering from a disease selected from the group consisting of: bicuspid aortic valve; a syndromic thoracic aortic aneurysm (TAA), or a non-syndromic TAA; and
wherein the iNOS inhibitor is selected from the group consisting of 1400W, L-NAME, GW274150, GW273629, Aminoguanidine (AG) hydrocloride, L-NIL and clotrimazole.

2. The method of claim 1 , wherein the patient is suffering from Marfan syndrome (MFS).

3. The method of claim 1 , wherein the patient is a human patient.

4. The method of claim 1 , wherein the proteoglycans are substrates of A Disintegrin And Metalloproteinase with Thrombospondin Motifs 1 (ADAMTS1).

5. The method of claim 4 , wherein the proteoglycans are selected from the group consisting of Aggrecan, versican, tissue factor pathway inhibitor-2 (TFPI-2), semaphorin 3C, nidogen-1, nidogen-2, desmocollin-3, dystroglycan, mac-2, Collagen type I, amphiregulin, TGF-α, heparin-binding EGF, Syndecan 4, versican neoepitopes and aggrecan neoepitopes.

6. The method of claim 1 , wherein the patient has decreased expression of ADAMTS1 relative to a patient without TAA.

7. The method of claim 1 , wherein the patient has Marfan syndrome.

8. The method of claim 1 , wherein progression of the thoracic aortic aneurysm (TAA) is prevented.

9. The method of claim 1 , wherein progression of the TAA is limited.

10. The method of claim 1 , wherein progression of the TAA is reverted.

11. The method of claim 1 , wherein the iNOS inhibitor is GW274150.

12. The method of claim 8 , wherein the iNOS inhibitor is GW274150.

13. The method of claim 1 , wherein the iNOS inhibitor is GW274150, and the patient has been diagnosed with Marfan Syndrome.

14. The method of claim 8 , wherein the iNOS inhibitor is GW274150, and the patient has been diagnosed with Marfan Syndrome.

15. The method of claim 1 , wherein the syndromic thoracic aortic aneurysm is selected from the group consisting of Marfan Syndrome, vascular Ehlers Danlos, Loeys Dietz Syndrome Type 1, Loeys Dietz Syndrome Type 2, and Familial thoracic aortic aneurysm and dissection.

16. The method of claim 9 , wherein the iNOS inhibitor is GW274150.

17. The method of claim 10 , wherein the iNOS inhibitor is GW274150.

Assignees

• Centro Nac De Investigaciones Cardiovasculares Carlos Iii F S P
• Consejo Superior Investigacion
• Univ Madrid Autonoma

Inventors

• Redondo Moya Juan Miguel
• Méndez-Barbero Nerea
• Oller Pedrosa Jorge
• Campanero García Miguel Ramón

Classifications

• G01N2800/329

  Diseases of the aorta or its branches, e.g. aneurysms, aortic dissection · CPC title

• C12Y114/13039

  Nitric-oxide synthase (NADPH dependent) (1.14.13.39) · CPC title

• G01N33/6893

  related to diseases not provided for elsewhere · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• G01N2333/96419

  Metalloendopeptidases (3.4.24) · CPC title