Rescue of glycogen storage disease Ia in mice by liver-directed therapies – Research Abstract

Hannah Baetge

Mentors: Mercedes Barzi, PhD, Karl-Dimiter Bissig, MD, PhD

Department of Pediatrics | Division of Genetics

Rescue of glycogen storage disease Ia in mice by liver-directed therapies

Glycogen Storage Disease Ia (GSD Ia) is a rare inherited metabolic disease caused by a deficiency in the G6PC1 gene, which codes for an important protein called glucose-6-phosphatase-alpha (G6Pase-alpha), primarily active in the liver. Without G6Pase-alpha, a key enzyme in gluconeogenesis, the patient is unable to break down glycogen into glucose. Consequently, GSD Ia patients experience low glucose levels, glycogen accumulation in the liver, and toxic metabolite build-up in other organs of the body including the kidney, intestines and in some cases the brain. Long-term implications may include liver cancer and end-stage kidney disease. The primary treatment option for GSD Ia involves a dietary approach; however, patients’ quality of life remains considerably compromised. Additionally, the dietary regimen does not provide a preventive measure against long-term complications. A viable gene therapy would significantly increase the quality of life of these patients, but it has yet to be found. One key obstacle in delivering gene therapy lies in hindrance caused by glycogen accumulation in the liver. To address this issue, we are focused on developing a solution comprised of a drug and gene-editing therapy using liver-specific G6pc-knockout mice. Through this approach, we hope to enhance gene editing efficiency for GSD Ia and come closer to a promising therapeutic solution for the victims of this debilitating disease.

References

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