mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease.
Nat Commun
; 12(1): 3090, 2021 05 25.
Article
in En
| MEDLINE
| ID: mdl-34035281
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Messenger
/
Genetic Therapy
/
Glycogen Storage Disease
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Glucose-6-Phosphatase
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Disease Models, Animal
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2021
Document type:
Article
Affiliation country: