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mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease

Abstract : Abstract Glycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α is critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) and carcinomas (HCCs). There is no treatment for GSD1a and the current standard-of-care for managing hypoglycemia (Glycosade ® /modified cornstarch) fails to prevent HCA/HCC risk. Therapeutic modalities such as enzyme replacement therapy and gene therapy are not ideal options for patients due to challenges in drug-delivery, efficacy, and safety. To develop a new treatment for GSD1a capable of addressing both the life-threatening hypoglycemia and HCA/HCC risk, we encapsulated engineered mRNAs encoding human G6Pase-α in lipid nanoparticles. We demonstrate the efficacy and safety of our approach in a preclinical murine model that phenotypically resembles the human condition, thus presenting a potential therapy that could have a significant therapeutic impact on the treatment of GSD1a.
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https://www.hal.inserm.fr/inserm-03257867
Contributor : Marie-Ange Di Carlo <>
Submitted on : Friday, June 11, 2021 - 10:45:56 AM
Last modification on : Saturday, June 12, 2021 - 3:23:18 AM

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Jingsong Cao, Minjung Choi, Eleonora Guadagnin, Maud Soty, Marine Silva, et al.. mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease. Nature Communications, Nature Publishing Group, 2021, 12 (1), pp.3090. ⟨10.1038/s41467-021-23318-2⟩. ⟨inserm-03257867⟩

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