2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Establishing preclinical efficacy for the first AAV gene therapy for GSD IX γ2 across stages of progressive liver disease

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The researchers aimed to characterize the progression of liver glycogen storage disease (GSD) IX γ2, a rare disorder caused by Phosphorylase Kinase (PhK) deficiency. They found that over 95% of patients with GSD IX γ2 developed liver fibrosis or cirrhosis, indicating a severe and progressive liver disease. Despite the life-threatening nature of the condition, there has been minimal research conducted.<br /><br />To address this, the researchers developed a mouse model of liver GSD IX γ2 and investigated the disease progression in this model. They discovered that the GSD IX γ2 mice exhibited significantly elevated levels of glycogen specific to the liver, confirming the relevance of the mouse model.<br /><br />Furthermore, the researchers observed that the GSD IX γ2 mice demonstrated progressive liver fibrosis as they aged. They also found that these mice had elevated disease biomarkers, which decreased with age.<br /><br />Based on these findings, the researchers suggest that AAV gene therapy could be a potential treatment for GSD IX γ2. They injected the GSD IX γ2 mice with AAV9-LSP-mPhkg2 at different ages to evaluate the efficacy of the gene therapy. The results of this study indicate that AAV gene therapy may serve as the first definitive treatment for GSD IX γ2. However, further studies are needed to evaluate the safety and determine the optimal therapeutic dose range for future clinical trials in humans.<br /><br />This research was made possible by funding from the National Institutes of Health. The researchers express their gratitude to the patients and families at Duke University who contributed to this study. Additionally, they acknowledge the prior research conducted on glycogen storage diseases type VI and IX and the deep phenotyping of liver glycogen storage disease IX.

Asset Subtitle

Presenting Author - Rebecca A. Gibson, PhD; Co-Author - Jeong-A Lim, PhD; Co-Author - Su Jin Choi, PhD; Co-Author - Neha Jumani, NA; Co-Author - Deeksha S. Bali, PhD, FACMG; Co-Author - Sarah P. Young, PhD, FACMG; Co-Author - William Jeck, MD, PhD; Co-Author - Baodong Sun, PhD; Co-Author - Aravind Asokan, PhD; Co-Author - Priya S. Kishnani, MD, FACMG;

Meta Tag

Biochemical genetics

Metabolic Disorder

Therapy

Co-Author Jeong-A Lim, PhD

Co-Author Su Jin Choi, PhD

Co-Author Neha Jumani, NA

Co-Author Deeksha S. Bali, PhD, FACMG

Co-Author Sarah P. Young, PhD, FACMG

Co-Author William Jeck, MD, PhD

Co-Author Baodong Sun, PhD

Co-Author Aravind Asokan, PhD

Co-Author Priya S. Kishnani, MD, FACMG

Presenting Author Rebecca A. Gibson, PhD

Keywords

liver glycogen storage disease

GSD IX γ2

Phosphorylase Kinase deficiency

liver fibrosis

cirrhosis

mouse model

glycogen

disease progression

gene therapy

AAV9-LSP-mPhkg2