Efficacy of Gene Therapy in Dogs with Glycogen Storage Disease Type Ia

Abstract

Glycogen storage diseases (GSD) are inherited metabolic disorders that affect glycogen use and storage. People with GSD Ia lack the enzyme glucose-6-phosphatase (G6Pase). As a result, these people are unable to convert liver glycogen to free glucose and develop severe hypoglycemia. Patients with GSD also develop growth retardation, hepatomegaly, renomegaly, hypertriglyceridemia, hypercholesterolemia, and hyperlactacidemia. No cure for GSD Ia currently exists. Patients are treated symptomatically with repeated naso-gastric feedings and glucose infusions to maintain normal blood glucose concentrations. Despite treatment, the underlying enzymatic defect remains. Gene therapy holds the promise of correcting this metabolic defect, thus providing a true cure for GSD Ia. Gene therapy uses modified virus particles to deliver a replacement functional G6Pase gene to the patient’s liver. Our group is using two viral vectors, adeno-associated virus (AAV) and helper-dependent adenovirus (HDAd), for gene therapy in dogs with an inheritable form of GSD Ia. We have treated three GSD Ia dogs with the AAV vector and two GSD Ia dogs with the HDAd vector. Vector-treated dogs were able to maintain normal blood glucose concentrations and unlike their untreated counterparts, survived for several years. These promising results provide hope that gene therapy may emerge as an effective treatment for people with GSD Ia.