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Nat Commun: mRNA therapy can treat hypoglycemia associated with glycogen storage disease and prevent liver cancer

 Last Update: 2021-05-31
 Source: Internet
 Author: User

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Glycogen storage disease (GSD) is a rare genetic disease characterized by abnormal enzymes in the process of glycogen metabolism, resulting in the inability to synthesize or decompose glycogen.

G6Pase-α is essential for maintaining euglycemia between meals.

GSD1a patients typically exhibit severe life-threatening low blood sugar disease and long-term liver complications, including liver cell adenoma (HCA) and hepatocellular carcinoma (HCC).

There is currently no treatment for GSD1a, and the current standard of care is: frequent feeding (every 4-6h) uncooked or modified corn starch, and overnight glucose gavage (mainly used for young patients).

prevention

Hypothetical model of hG6PC mRNA treatment

In this study, the researchers encapsulated the engineered mRNA encoding human G6Pase-α in lipid nanoparticles (LNPs) to develop new mRNA therapies for GSD1a.

Researchers encapsulate engineered mRNA encoding human G6Pase-α in lipid nanoparticles (LNPs) to develop new mRNA therapies for GSD1a.

The levels of hG6PC mRNA and hG6Pase-α protein in the liver of wild-type mice and their active half-life

The results showed that the effectiveness and safety of the method was confirmed in a preclinical mouse model phenotypically similar to human diseases.

Researchers have shown that the mRNA therapy can be used to treat life-threatening hypoglycemia and reduce the long-term high risk of HCA/HCC associated with this disease.

org/10.

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