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

Jingsong Cao; Minjung Choi; Eleonora Guadagnin; Maud Soty; Marine Silva; Vincent Verzieux; Edward Weisser; Arianna Markel; Jenny Zhuo; Shi Liang; Ling Yin; Andrea Frassetto; Anne-Renee Graham; Kristine Burke; Tatiana Ketova; Cosmin Mihai; Zach Zalinger; Becca Levy; Gilles Besin; Meredith Wolfrom; Barbara Tran; Christopher Tunkey; Erik Owen; Joe Sarkis; Athanasios Dousis; Vladimir Presnyak; Christopher Pepin; Wei Zheng; Lei Ci; Marjie Hard; Edward Miracco; Lisa Rice; Vi Nguyen; Mike Zimmer; Uma Rajarajacholan; Patrick Finn; Gilles Mithieux; Fabienne Rajas; Paolo Martini; Paloma Giangrande

doi:10.1038/s41467-021-23318-2

Journal Articles Nature Communications Year : 2021

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

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Jingsong Cao

Function : Author

Rare Diseases [Cambridge, MA, USA]

Minjung Choi

Function : Author

Rare Diseases [Cambridge, MA, USA]

Eleonora Guadagnin

Function : Author

Rare Diseases [Cambridge, MA, USA]

Maud Soty

Function : Author

Nutrition, diabète et cerveau

Marine Silva

Function : Author

Nutrition, diabète et cerveau

Vincent Verzieux

Function : Author

Nutrition, diabète et cerveau

Edward Weisser

Function : Author

Rare Diseases [Cambridge, MA, USA]

Arianna Markel

Function : Author

Rare Diseases [Cambridge, MA, USA]

Jenny Zhuo

Function : Author

Rare Diseases [Cambridge, MA, USA]

Shi Liang

Function : Author

Rare Diseases [Cambridge, MA, USA]

Ling Yin

Function : Author

Rare Diseases [Cambridge, MA, USA]

Andrea Frassetto

Function : Author

Rare Diseases [Cambridge, MA, USA]

Anne-Renee Graham

Function : Author

Platform [Cambridge, MA, USA]

Kristine Burke

Function : Author

Platform [Cambridge, MA, USA]

Tatiana Ketova

Function : Author

Platform [Cambridge, MA, USA]

Cosmin Mihai

Function : Author

Platform [Cambridge, MA, USA]

Zach Zalinger

Function : Author

Platform [Cambridge, MA, USA]

Becca Levy

Function : Author

Platform [Cambridge, MA, USA]

Gilles Besin

Function : Author

Platform [Cambridge, MA, USA]

Meredith Wolfrom

Function : Author

Platform [Cambridge, MA, USA]

Barbara Tran

Function : Author

Platform [Cambridge, MA, USA]

Christopher Tunkey

Function : Author

Platform [Cambridge, MA, USA]

Erik Owen

Function : Author

Platform [Cambridge, MA, USA]

Joe Sarkis

Function : Author

Platform [Cambridge, MA, USA]

Athanasios Dousis

Function : Author

Platform [Cambridge, MA, USA]

Vladimir Presnyak

Function : Author

Platform [Cambridge, MA, USA]

Christopher Pepin

Function : Author

Platform [Cambridge, MA, USA]

Wei Zheng

Function : Author
PersonId : 756070
ORCID : 0000-0003-1226-070X

Platform [Cambridge, MA, USA]

Lei Ci

Function : Author

Platform [Cambridge, MA, USA]

Marjie Hard

Function : Author

Platform [Cambridge, MA, USA]

Edward Miracco

Function : Author

Platform [Cambridge, MA, USA]

Lisa Rice

Function : Author

Rare Diseases [Cambridge, MA, USA]

Vi Nguyen

Function : Author

Rare Diseases [Cambridge, MA, USA]

Mike Zimmer

Function : Author

Rare Diseases [Cambridge, MA, USA]

Uma Rajarajacholan

Function : Author

Rare Diseases [Cambridge, MA, USA]

Patrick Finn

Function : Author

Rare Diseases [Cambridge, MA, USA]

Gilles Mithieux

Function : Author
PersonId : 758622
ORCID : 0000-0003-3579-8529
IdRef : 034018778

Nutrition, diabète et cerveau

Fabienne Rajas

Function : Author
PersonId : 758623
ORCID : 0000-0002-9233-7633
IdRef : 082345775

Nutrition, diabète et cerveau

Paolo Martini

Function : Author

Rare Diseases [Cambridge, MA, USA]

Paloma Giangrande

Function : Correspondent author
PersonId : 1101915

Connectez-vous pour contacter l'auteur

Rare Diseases [Cambridge, MA, USA]

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.

Domains

Life Sciences [q-bio] Neurons and Cognition [q-bio.NC]

Fichier principal

s41467-021-23318-2.pdf (3.91 Mo)

Origin : Publication funded by an institution

Marie-Ange Di Carlo : Connect in order to contact the contributor

https://www.hal.inserm.fr/inserm-03257867

Submitted on : Friday, June 11, 2021-10:45:56 AM

Last modification on : Friday, September 30, 2022-11:50:06 AM

Dates and versions

inserm-03257867 , version 1 (11-06-2021)

Identifiers

HAL Id : inserm-03257867 , version 1
DOI : 10.1038/s41467-021-23318-2
PUBMED : 34035281
PUBMEDCENTRAL : PMC8149455

Cite

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, 2021, 12 (1), pp.3090. ⟨10.1038/s41467-021-23318-2⟩. ⟨inserm-03257867⟩

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

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