Low dose M021, a novel recombinant human acid alpha-glucosidase (GAA) enzyme, is significantly more effective than high dose alglucosidase alfa in reducing accumulated glycogen in the muscles, according to the results of a new study conducted of a mouse model of Pompe disease presented at the 18th Annual WORLDSymposium 2022.

“These promising results suggest that M021 warrants further development as a potential next-generation treatment for Pompe disease,” the authors wrote.

“We plan to complete efficacy evaluations of M021 in mice and hope to advance this potential therapeutic approach to future clinical studies,” Russell Gotschall, vice president of research and development at M6P Therapeutics said in a press release.

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Pompe disease is characterized by the deficiency of the GAA enzyme, which is responsible for breaking down glycogen into glucose. Enzyme replacement therapy is currently the only disease-modifying therapy for patients with Pompe disease.

Read more about Pompe disease therapies

However, with time, the patients’ bodies tend to develop neutralizing antibodies against the enzyme reducing the effectiveness of the treatment. Research, therefore, continues into new treatments for the disease.

M021 is coexpressed with S1S3 phosphotransferase. This greatly increases the levels of mannose 6-phosphate of the recombinant human GAA in the production cell line, thereby allowing the production of M021 with high amounts of bis-phosphorylated glycans. This in turn increases its binding affinity for the cation-independent mannose-6-phosphate receptor.

Finally, M021 has low levels of neutral oligosaccharides, therefore maximizing cation-independent mannose-6-phosphate receptor targeting and minimizing unproductive mannose receptor and asialoglycoprotein receptor clearance in the liver.

These properties potentially translate into an optimal pharmacokinetic profile and better biodistribution to target muscles., the authors said. This, in turn, would lead to more effective glycogen reduction.


Gotschall R, Liu L, Gray K, et al. M021: A uniquely glycosylated, highly phosphorylated acid-alpha glucosidase enzyme replacement therapy for the treatment of Pompe disease. Mol Genet Metab. 2022;135(2):S50. doi:10.1016/j.ymgme.2021.11.121

M6P Therapeutics presents promising preclinical data in lysosomal storage disorders at the 18th Annual WORLDSymposium™ 2022. News release. M6P Therapeutics; February 11, 2022.