New method to treat acidosis related diseases

The present invention relates to the treatment of acidosis related diseases. In this study, the inventors have investigated how human monocytes adapt, survive and differentiate into macrophages under lactic acidosis. Experiments were conducted under atmospheric oxygen and in the presence of glucose, to rule out an effect of oxygen or glucose deprivation. Prolonged exposure to LA affected monocyte/macrophage metabolism. Extracellular acidosis induced mitochondrial membrane depolarization and significantly decreased nutrient consumption, resulting in a dependence of the macrophages on a transient phase of autophagy for survival. In fasting conditions, hepatocytes produce the ketone bodies acetoacetate (AcAc) and ?-hydroxybutyrate (?-OHB) that constitute alternative fuel for extrahepatic cells. The inventors found here that AcAc protected the mitochondria from acidosis-induced depolarization and mitophagy, allowing the cells to continue to metabolize nutrients, thereby avoiding the need for self-catabolism to survive. Acetoacetate therefore appears to be a crucial alternative fuel metabolite of potential therapeutic interest to increase tissue tolerance to lactic acidosis. Thus, the invention relates to the acetoacetate (AcAc) for use in the treatment of acidosis related diseases.

Keywords: Acetoacetate, Acidosis
Patent Application number: European Procedure (Patents) (EPA) - 08 Juil. 2021 - 21305941.3
Inventors:
DELNESTE YvesASFAR PierreBEAUVILLAIN CélineJEANNIN PascalePROCACCIO Vincent
Publications:
Nat Commun. 2021 Dec 8;12(1):7115. doi: 10.1038/s41467-021-27426-x

Reference:

BIO19221-T1

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Patent filling date: 2022-07-07

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