Transcriptomic gene analysis of skeletal muscle biopsies from patients with late-onset Pompe disease (LOPD) suggests that enzyme replacement therapy attenuates the expression of dysregulated genes involved in lysosomal function, according to a recently published study in Molecular Genetics and Metabolism.

Although enzyme replacement therapy has significantly improved the survival and quality of life of many patients with PD, additional disease phenotypes, with clinical manifestations ranging from dysphagia to learning disabilities, have come to light, which means that there are several challenges remaining in the management of this disease.

Read more about PD therapies

Continue Reading

To further understand the underlying mechanisms behind PD and how they react to enzyme replacement therapy, the authors performed a transcriptomic analysis of skeletal muscle biopsies from 8 patients with LOPD receiving avalglucosidase alfa in the context of a phase 1 clinical trial, which was later compared to that of 10 healthy controls.

There was a significant difference between the global gene expression of patients with PD and healthy controls, with the former having a significant upregulation in several of the studies’ gene probes. After treatment with avalglucosidase alfa, over 50% of those probes decreased 1- to 2-fold.

“Prior to the initiation of treatment, LOPD patients exhibit substantial dysregulation of transcript expression compared to controls,” the authors wrote. “Following 6 months of [enzyme replacement therapy] with avalglucosidase alfa, there was a modest attenuation of expression.”

Importantly, although PD is not typically associated with inflammation and immune cell infiltration, dysregulation in inflammatory pathways was noted in the study.

Enzyme replacement therapy had a strong attenuating effect on dysregulated genes after 6 months of treatment. The authors noted that patients with a higher percentage of dysregulated genes had stronger gene attenuation after treatment.

 “Our analysis further highlights the positive effect of treatment with avalglucosidase alfa attenuating the transcriptional dysregulation observed in LOPD patients,” the authors wrote.


Kinton S, Dufault MR, Zhang M, George K. Transcriptomic characterization of clinical skeletal muscle biopsy from late-onset Pompe patients. Mol Genet Metab. Published online January 25, 2023. doi:10.1016/j.ymgme.2023.107526