mRNA replacement therapy for GSD-Ib

Glycogen storage disease type Ib (GSD-Ib) is caused by deficiency of glucose-6-phosphate transporter (G6PT), an inborn error of metabolism presenting with glucose abnormalities, neutropenia, renal disease and increased risks of hepatic adenomas and hepatocellular carcinoma. More effective treatments are highly needed and while gene therapy holds great potential risks of liver cancer, lack of correction of renal and myeloid defects, and loss of long-term transgene expression in growing children are important hurdles. 

In this proposal, we will investigate the efficacy of repeated injections of mRNA encoding G6PT in G6pt^−/−mice, a model that recapitulates the phenotype of human GSD-Ib. The efficacy will be evaluated through well-established and clinically relevant endpoints of liver, kidney, and neutrophil functions.

Encouraging preclinical data generated in other inborn errors of metabolism, including glycogen storage disease type Ia, have led to clinical trials and we expected that the results generated through this proposal will also pave the way towards a clinical trial for GSD-Ib.