Compositions and methods for reducing cellular fat and for...

G - Physics – 01 – N

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G01N 33/53 (2006.01) C12N 15/09 (2006.01) C12P 13/22 (2006.01)

Patent

CA 2643846

Methods are disclosed for determining whether organ toxicity, particularly cardiotoxicity, will occur in a patient selected for treatment with various kinase inhibitors, such as tyrosine kinase inhibitors, more particularly erbB inhibitors such as Herceptin. In addition, methods are disclosed for determining whether a potential drug is likely to produce a cardiotoxic effect. The methods involve analyzing lipid levels or the expression fatty acid oxidation enzymes, pAMP activated protein kinase, glucose uptake, to determine whether a fatty acid oxidation disorder is present. The identification of a fatty acid oxidation disorder can be used as a predictor of toxicity, especially cardiac toxicity, and as an indication that organ function should be carefully monitored if a drug such as a tyrosine kinase inhibitor is administered. Methods are also disclosed for protecting organs from metabolic stress and for the treatment of cells, such as adipocytes, to reduce their lipid content.

L'invention concerne des procédés permettant de déterminer si une toxicité organique, en particulier une cardiotoxicité, est susceptible de se manifester chez un patient candidat au traitement avec divers inhibiteurs de kinases, par exemple des inhibiteurs de tyrosine kinases, plus particulièrement des inhibiteurs d'erbB tels que l'herceptine. Elle concerne en outre des procédés permettant de déterminer si un médicament potentiel est susceptible de produire un effet cardiotoxique. Ces procédés comprennent l'analyse des taux de lipides ou de l'expression d'enzymes oxydant les acides gras, de la protéine kinase activée par le pAMP, de l'absorption de glucose, afin de déterminer si un trouble lié à l'oxydation d'acides gras est présent. L'identification d'un trouble lié à l'oxydation d'acides gras peut servir de prédicteur de la toxicité, en particulier de la toxicité cardiaque, et d'indication qu'une fonction organique doit être contrôlée avec soin si un médicament tel qu'un inhibiteur de tyrosine kinase est administré. L'invention concerne également des procédés permettant de protéger des organes contre le stress métabolique et des procédés de traitement de cellules, par exemple des adipocytes, afin d'en réduire le contenu lipidique.

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