Mechanisms of myoblast transfer in treating heart failure

C - Chemistry – Metallurgy – 12 – N

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C12N 5/10 (2006.01) A61K 35/14 (2006.01) A61K 38/13 (2006.01) A61K 48/00 (2006.01) C12N 15/85 (2006.01)

Patent

CA 2495112

Bioengineering the regenerative heart provides a novel treatment for heart failure. On May 14, 2002, a 55-year-old man suffering ischemic myocardial infarction received 25 injections carrying 465 million cGMP-produced pure myoblasts into his myocardium after coronary artery bypass grafting. Three myogenesis mechanisms were elucidated with 17 human/porcine xenografts using cyclosporine as immunosuppressant. Some myoblasts developed to become cardiomyocytes. Others transferred their nuclei into host cardiomyocytes through natural cell fusion. As yet others formed skeletal myofibers with satellite cells. De novo production of contractile filaments augmented heart contractility. Human myoblasts transduced with VEGF165 gene produced six times more capillaries in porcine myocardium than placebo. Xenograft rejection was not observed for up to 20 weeks despite cyclosporine discontinuation at 6 weeks.

L'invention concerne un nouveau traitement de l'insuffisance cardiaque mis au point par le génie biologique en vue de régénérer le coeur. Le 14 mai 2002, un homme âgé de 55 ans atteint d'infarctus du myocarde ischémique a reçu dans le myocarde 25 injections comportant 465 millions de myoblastes <i>purs</i> produits par cGMP, après pontage aortocoronarien. Trois mécanismes de myogenèse ont été élucidés grâce à 17 xénogreffes homme/porc utilisant de la cyclosporine comme immunosuppresseur. Certains myoblastes se sont développés en cardiomyocytes. D'autres ont transféré leurs noyaux dans des cardiomyocytes hôtes par fusion cellulaire naturelle. D'autres encore ont formé des myofibres squelettiques avec des cellules satellites. La nouvelle production de filaments contractiles a permis d'augmenter la contractilité du coeur. Des myoblastes humains transduits à l'aide du gène VEGF¿165? ont produit six fois plus de capillaires dans un myocarde de porc que le placebo. Aucun rejet de greffe n'a été observé jusqu'à 20 semaines, malgré l'interruption de la cyclosporine à 6 semaines.

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