Resumen
[0001] 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). [0002] La présente invention concerne un procédé in vitro de dépistage de sujets présentant un risque de développer un anévrisme de l'aorte thoracique (AAT) ou une maladie provoquant un AAT, ledit procédé consistant à : (a) mesurer le motif ou le taux d'expression d'au moins une ADAMTS1 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs 1) présente dans un échantillon biologique isolé prélevé chez les sujets à dépister ; et (b) comparer ledit motif ou taux d'expression de ladite ADAMTS1 des sujets à dépister avec un motif ou taux d'expression déjà établi, l'expression réduite de ladite ADAMTS1 étant indicatrice d'un anévrisme de l'aorte thoracique (AAT).
Reivindicaciones
1. A composition comprising an iNOS (inducible nitric oxide synthase) inhibitor for use in the prophylactic or therapeutic treatment of a thoracic aortic aneurysm (TAA) in a human patient, wherein the iNOS inhibitor is selected from the group consisting of 1400W (N'-[[3-(aminomethyl)phenyl]methyl]ethanimidamide), GW274150 ((2S)-2-amino-4-[2-(1-aminoethylideneamino)ethylsulfanyl]butanoic acid), GW273629 ((2R)-2-amino-3-[2-(1-aminoethylideneamino)ethylsulfonyl]propanoic acid), Aminoguanidine (AG) (2-aminoguanidine), L-NIL ((2S)-2-amino-6-(1-aminoethylideneamino)hexanoic acid), clotrimazole and L-NAME (methyl (2S)-2-amino-5-[[amino(nitramido)methylidene]amino]pentanoate), or any pharmaceutically acceptable salts thereof. 2. The composition for use according to claim 1, wherein the iNOS inhibitor is selected from the group consisting of GW274150 ((2S)-2-amino-4-[2-(1-aminoethylideneamino)ethylsulfanyl]butanoic acid), GW273629 ((2R)-2-amino-3-[2-(1-aminoethylideneamino)ethylsulfonyl]propanoic acid), Aminoguanidine (AG) (2-aminoguanidine), and clotrimazole, or any pharmaceutically acceptable salts thereof. 3. The composition for use according to claim 1 or 2, wherein the iNOS inhibitor is GW274150, or any pharmaceutically acceptable salts thereof. 4. The composition for use according to any of claims 1 to 3, wherein the patient is suffering from a disease selected from the list consisting of bicuspid aortic valve; a syndromic thoracic aortic aneurysm (TAA) such as Marfan Syndrome, vascular Ehlers Danlos, Loeys Dietz Syndrome (Types 1 and 2), and Familial thoracic aortic aneurysm and dissection (familial TAAD), a non-syndromic TAA. 5. The composition for use according to claim 4 wherein the patient is suffering from Marfan syndrome (MFS). 6. The composition for use according to any of the claims 1 to 3, wherein such use is in a medical therapy directed at preventing, limiting and reverting the progressive TAA expansion in syndromic and non-syndromic presentations of the disease. 7. The composition for use according to any of claims 1 to 3, wherein such use is in a medical therapy directed at preventing, limiting or reverting the progression of the thoracic aortic aneurysm (TAA). 8. The composition for use according to claim 7, wherein the progression of the thoracic aortic aneurysm (TAA) is limited or reverted. 9. The composition for use according to any of claims 6 to 8, wherein the syndromic presentation of the disease is Marfan syndrome.
