4.5 Review

Therapeutic thoroughfares for adults living with Pompe disease

Related references

Note: Only part of the references are listed.
Meeting Abstract Endocrinology & Metabolism

In-vitro characterization of MZE001, an orally active GYS1 inhibitor to treat Pompe disease

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Gene Therapy Developments for Pompe Disease

Zeenath Unnisa et al.

Summary: Pompe disease is a genetic neuromuscular disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). While enzyme replacement therapy has limitations, gene therapies using adeno-associated virus (AAV) and lentiviral vector (LV) show potential in treating this disorder. Improved preclinical efficacy and safety data have been achieved by optimizing viral vector designs for tissue-specific expression and GAA protein modifications.

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Mazen M. Dimachkie et al.

Summary: The long-term safety and efficacy of Avalglucosidase alfa in adult patients with late-onset Pompe disease has been studied for up to 6.5 years, and the results show that it is generally well tolerated and effective.

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Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease

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Summary: This study demonstrates that avalglucosidase alfa is safe and effective for long-term use in patients with late-onset Pompe disease.

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Summary: Pompe disease is a rare disorder characterized by muscle and respiratory function loss. The current treatment with alglucosidase alfa lacks efficacy, while a novel therapy combining a recombinant enzyme and a stabilizer may offer improved outcomes in patients with late-onset Pompe disease.

LANCET NEUROLOGY (2021)

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Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial

Jordi Diaz-Manera et al.

Summary: In this study, treatment with avalglucosidase alfa showed clinically meaningful improvement in respiratory function, ambulation, and functional endurance compared to alglucosidase alfa, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa.

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Summary: The study engineered AAV vectors by incorporating short DNA oligonucleotides to antagonize TLR9 activation, reducing innate immune responses and enhancing gene expression in clinically relevant animal models. The engineered vectors can avoid adverse reactions in some models, demonstrating a potential wider therapeutic window for AAV therapies.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Hepatic expression of GAA results in enhanced enzyme bioavailability in mice and non-human primates

Helena Costa-Verdera et al.

Summary: Hepatic-directed gene therapy with adeno-associated virus (AAV) vectors enhances bioavailability of acid alpha-glucosidase (GAA) compared with enzyme replacement therapy (ERT), resulting in improved rescue of Pompe disease phenotype in mice and broad enzyme distribution in mice and non-human primates.

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Carrier frequency and predicted genetic prevalence of Pompe disease based on a general population database

Kyung Sun Park

Summary: The study estimated the genetic prevalence of Pompe disease using the Genome Aggregation Database and various locus-specific databases. East Asian and African populations showed higher proportions of pathogenic or likely pathogenic variants associated with classic infantile-onset Pompe disease. The overall carrier frequency and predicted genetic prevalence for Pompe disease were 1.3% and 1:23,232, respectively, with variability observed across different populations.

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Summary: Pompe disease is a lysosomal and neuromuscular disorder caused by a deficiency of acid alpha-glucosidase (GAA). Biochemical diagnosis is crucial and fibroblasts using 4MUG as a substrate proved to be the most reliable assay, allowing the differentiation of phenotypes and ruling out pseudodeficiencies caused by GAA variants.

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Lentiviral Hematopoietic Stem Cell Gene Therapy Rescues Clinical Phenotypes in a Murine Model of Pompe Disease

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Newborn screening: Taiwanese experience

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Liver depot gene therapy for Pompe disease

Priya S. Kishnani et al.

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Improved efficacy of a next-generation ERT in murine Pompe disease

Su Xu et al.

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A Randomized Study of Alglucosidase Alfa in Late-Onset Pompe's Disease.

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