A novel molecule may be superior to already existent treatment compounds for Pompe Disease (PD), according to a study recently published in Molecular Genetics and Metabolism.

“It does so more effectively than existing PCTs in vitro, in cellular and in vivo in zebrafish, thus representing a superior therapeutic alternative to Miglustat® for Pompe disease,” the authors wrote.

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New research has identified 1,6-epi-cycophellitol cyclosulfamidate as a potential stabilizer for recombinant human alpha-glucosidase, the researchers noted. This enzyme is deficient in the pathogenesis of PD, a disease that, to this date, has only a single treatment approach: enzyme replacement therapy (ERT), they added.

Although effective, ERT is a complex practice that still faces many challenges, the study team said. In the case of PD, the recombinant human GAA that patients with PD receive is widely unstable in plasma. Since this enzyme functions inside lysosomes, especially in muscle cells, its delivery inside these intracellular structures is important to guarantee treatment efficacy. Because the transport of the enzyme alone is suboptimal, stabilizers, known as reversible small pharmacological chaperones, are part of the formulation, the investigators continued.

For example, N-butyldeoxynojirimycin is part of a drug named Miglustat® currently in phase 2 and 3 clinical trials. Arguably 1 of the biggest downsides of this combination is that the chaperone lacks selectivity and is able to bind to other enzymes, such as β-glucosidase GBA2 and glucosylceramide synthase, which may lead to unwanted effects, the study team noted.

Notably, 1,6-epi-cycophellitol cyclosulfamidate targets recombinant human GAA with marked selectivity above other carbohydrate processing enzymes. The researchers further observed the optimal transport capacity of GAA into lysosomes, even in vivo experiments.

Although more research is needed to test 1,6-epi-cycophellitol cyclosulfamidate as an ERT compound, these results bring hope to patients with PD, a disease of great morbidity, the authors noted.

“This metabolic disease is characterized by lysosomal accumulation of glycogen which provokes progressive apoptosis in skeletal and cardiac muscle cells, causing muscle hypotonia, loss of respiratory and cardiac motor functions, ultimately affecting the liver and the nervous system in severe cases,” the authors highlighted.


Artola M, Aerts J. 1,6-epi-cyclophellitol cyclosulfamidate is a new superior lysosomal α-glucosidase stabilizer for the treatment of Pompe disease. Mol Genet Metab. Published online February 2023. doi:10.1016/j.ymgme.2022.107007