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AssigneesInstitut National de la Sante et de la Recherche Medicale, Assistance Publique-HôPitaux De Paris (Aphp), Centre National De La Recherche Scientifique, Université Paris Cité, College De France
InventorsStéphane GERMAIN, Nicolas BRECHOT
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The disruption of endothelial barrier integrity leading to increased vascular permeability contributes to many pathological processes. In a first cohort of 11 patients having cardiac arrest with vascular leakage, the inventors identified that AREG is 56-fold more expressed than control. During a second prospective clinical study, they confirmed a strong association between the plasma level of AREG and the fluid balance in 77 independent patients hospitalized for a cardiogenic shock. The inventors finally showed a crucial role for this protein in Areg−/− mice, with i) no KO-mice achieving a return of spontaneous circulation (ROSC) vs. 40% in WT mice (n=6 per group, p<0.05) and ii) a beneficial effect of 10 μg recombinant AREG i.v. injection at the time of resuscitation, with 80% injected mice that achieve a ROSC vs 40% in controls (n=6, p<0.05). Finally, using markers of vascular extravasation, they demonstrated that AREG administration was decreasing the level of vascular leakage. The results thus indicate that administering AREG in a patient suffering from vascular permeability would be beneficial. Thus, the present invention relates to the use of amphiregulin (AREG) in methods of treating vascular permeability.
A method of treating vascular hyperpermeability in a patient in need thereof comprising administering to the patient a therapeutically effective amount of i) an AREG polypeptide or ii) a polynucleotide encoding the AREG polypeptide.
The method of claim 8 wherein the shock is selected from the group consisting of circulatory shock, cardiogenic shock, ischemic shock, hypervolemic shock, hemorrhagic shock, and septic shock.
A method of treating an ischemic condition in a patient in need thereof comprising the steps consisting of i) restoring blood supply in ischemic tissue, and ii) preserving vascular endothelial cell barrier integrity of said ischemic tissue by administering to said patient a therapeutically effective amount of an AREG polypeptide or a polynucleotide encoding the AREG polypeptide, where steps i) and ii) are performed sequentially or concomitantly.
Dependencies are inferred from the claim text.