Maintenance of smooth muscle integrity by morphogenic proteins

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/86 (2006.01) A61K 38/18 (2006.01) C07K 14/47 (2006.01) C07K 14/51 (2006.01) A61K 38/00 (2006.01) A61K 48/00 (2006.01)

Patent

CA 2314423

Disclosed are compositions and methods for maintaining the integrity of smooth muscle, particularly vascular smooth muscle. Vascular diseases are characterized by an excessive build-up of vascular smooth muscle cells, resulting in an occlusion of a blood vessel, and/or by loss of elasticity in the blood vessels. Causes of blood vessel occlusion include smooth muscle cell proliferation and inflammatory responses. Inhibition of the proliferation of smooth muscle cells or inflammatory responses represents an effective treatment for vascular disorders, such as atherosclerosis and restenosis. Treatment may include administration of a morphogenic protein. The protein itself may be delivered to the site of vascular occlusion or the protein may be delivered by a vector, such as an adenoviral vector containing a DNA insert encoding a morphogenic protein. Such compositions and methods may also inhibit the responses of smooth muscle cells to various traumas, such as exposure to toxic agents. All of these treatmetns operate to preserve the cell phenotype by inhibiting an increase in extracellular matrix proteins, such as collagen, or by maintaining the normal balance of extracellular matrix proteins, such as Types I and III collagen.

L'invention concerne des compositions et des procédés servant à entretenir l'intégrité de muscles lisses, en particulier de muscles lisses vasculaires. Les maladies vasculaires sont caractérisées par une accumulation excessive de cellules de muscles lisses vasculaires qui a pour conséquence l'occlusion d'un vaisseau sanguin, et/ou par une perte d'élasticité des vaisseaux sanguins. Des causes d'occlusion de vaisseaux sanguins comprennent notamment une prolifération de cellules de muscles lisses et des réactions inflammatoires. Une inhibition de la prolifération de cellules de muscles lisses ou de réactions inflammatoires constitue un traitement efficace de troubles vasculaires tels que l'athérosclérose et la resténose. Le traitement peut comporter l'administration d'une protéine morphogénique. La protéine elle-même peut être administrée au site d'occlusion vasculaire, ou peut être administrée par un vecteur, tel qu'un vecteur adénoviral contenant un insert d'ADN codant pour une protéine morphogénique. Ces compositions et procédés peuvent également inhiber les réactions de cellules de muscles lisses à divers traumatismes, telle qu'une exposition à des agents toxiques. Tous ces traitements servent à préserver le phénotype de la cellule par l'inhibition d'une augmentation de protéines de matrice extracellulaire, tel le collagène, ou par l'entretien de l'équilibre normal de protéines de matrice extracellulaire, tels les collagènes de type I et III.

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