A study published in Chemical Science found that attaching a ligand that is recognized by a specific receptor in the cellular transport system to the acid alpha-glucosidase (GAA) enzyme increases the effectiveness of enzyme replacement therapy in Pompe disease. 

Lai-Xi Wang, the corresponding author of the study, said, “This work holds great promise for a better, less costly treatment of the life-threatening Pompe disease.”

Enzyme replacement therapy, where large amounts of the missing GAA enzyme are injected into the body, is the only treatment available for Pompe disease. However, this is a highly inefficient approach, as only a small amount of the enzyme reaches cells to perform its role of breaking down glycogen into glucose.

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Wang stated, “We have developed a simple method of modifying the enzyme that demonstrated much-enhanced receptor binding, cellular uptake, and glycogen degrading activity in cells.”

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Wang and his team discovered the ligand while studying the chemical synthesis and binding properties of various molecules. They then developed a method to attach it to the GAA enzyme. Using cell culture experiments, they demonstrated that the delivery of the enzyme replacement therapy to the cellular machinery where it was needed was a much more efficient method. 

Xiao Zhang, PhD, the first author of the study, stated, “Our method could dramatically reduce the amount of enzyme and maybe also the frequency of injections needed to treat Pompe disease.”

The researchers are now testing the GAA-ligand therapy in animal models of Pompe disease, and they are hoping to test it in clinical trials in the future.

Pompe disease is a rare genetic disease characterized by a deficiency or absence of the GAA enzyme. It can affect the skeletal muscles and the heart, and can be fatal if left untreated. 


UMD-led study could offer hope to Pompe disease patients. News release. University of Maryland: College of Computer, Mathematical, and Natural Sciences; August 19, 2021.