Regulation of autophagy and cell survival

A - Human Necessities – 61 – K

Patent

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A61K 31/713 (2006.01) A61K 31/138 (2006.01) A61K 31/4706 (2006.01) A61K 31/675 (2006.01) A61P 35/00 (2006.01) C12Q 1/02 (2006.01)

Patent

CA 2595156

Methods of treating an individual who has been identified as having glycolysis dependent cancer are disclosed. The methods comprise the step of: administering to suc an individual a combination of an anti-cancer composition that renders the cancer incapable of glycolysis and an autophagy inhibitor. Pharmaceutical compositions and kits comprising that renders the cancer incapable of glycolysis and an autophagy inhibit are also disclosed. Methods of treating an individual who has a disease characterized b cell degeneration and cell death due to autophagy are disclosed. The methods comprise administering to the individual a permeable form of a metabolic substrate that can be oxidized in the tricarboxylic acid cycle to produce NADH. Methods for identifying an autophagy inhibitor comprising performing a test assay using an apopto sis-resistant cell are disclosed.

L'invention concerne des méthodes permettant de traiter un individu chez lequel un cancer dépendant de la glycolyse a été diagnostiqué. Ces méthodes comprennent les étapes qui consistent à: administrer à un tel individu une combinaison d'une composition anticancéreuse bloquant la capacité de glycolyse du cancer, et d'un inhibiteur de l'autophagie. L'invention concerne également des compositions pharmaceutiques et des trousses comprenant ces compositions, destinées à bloquer la capacité de glycolyse du cancer et à inhiber l'autophagie. Des méthodes permettant de traiter un individu présentant une maladie se caractérisant par une dégénération cellulaire, et par la mort cellulaire due à l'autophagie, sont également décrites. Ces méthodes consistent à administrer à l'individu une forme perméable d'un substrat métabolique qui peut être oxydé dans le cycle d'acide tricarboxique, afin de produire du NADH. Enfin, l'invention concerne des procédés permettant d'identifier un inhibiteur de l'autophagie, consistant à effectuer un test à l'aide d'une cellule résistante à l'apoptose.

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