Thrombospondin-1 derived peptides and treatment methods

A - Human Necessities – 61 – K

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A61K 38/00 (2006.01) C07K 2/00 (2006.01) C07K 4/00 (2006.01) C07K 5/00 (2006.01) C07K 7/00 (2006.01) C07K 14/00 (2006.01) C07K 16/00 (2006.01) C07K 17/00 (2006.01)

Patent

CA 2613193

Treatments employing the matricellular protein thrombospondin-1 (TSP-I) and related compositions are disclosed for stabilizing atherosclerotic plaque and decreasing occurrence of plaque rupture events leading to, for example, myocardial infarction, stroke, and acute limb ischemia. Various peptides, including certain synthetic peptides, related to TSP-I are also disclosed. Such peptides have utility in stabilizing plaque in various contexts, including the disease states mentioned above. Some of these peptides include one or more sequences related to active sites of TSP-I for regulating, e.g., TGF-.beta.l and MMP-9 activity. Experimental data show that a representative peptide provides a beneficial effect with systemic injection of the peptide.

L'invention concerne des traitements utilisant la thrombospondine-1 (TSP-1), une protéine matricellulaire, et des compositions associées permettant de stabiliser la plaque athéroscléreuse et de réduire le nombre d'événements de rupture de plaque provoquant, par exemple, un infarctus du myocarde, un accident vasculaire cérébral et une ischémie aiguë de membres. L'invention se rapporte également à divers peptides, y compris certains peptides synthétiques, associés à la TSP-1. Ces peptides sont utiles pour stabiliser la plaque dans divers contextes, y compris lors des problèmes de santé susmentionnés. Certains de ces peptides contiennent une ou plusieurs séquences relatives à des sites actifs de la TSP-1 pour réguler, p. ex. l'activité du TGF-ß1 et de la MMP-9. Des données expérimentales indiquent qu'un peptide représentatif possède un effet bénéfique en injection systémique.

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