#South Korea #GC Biopharma #Yongin #Hunterase #Idursulfase beta

GC Biopharma's Breakthrough Study on Hunterase Delivery Mechanism

On August 21, 2025, GC Biopharma, a prominent global pharmaceutical firm based in South Korea, announced significant findings regarding the viability of Hunterase (idursulfase beta) as a treatment for Hunter syndrome (MPS II). This pivotal research, published in the International Journal of Biological Macromolecules, illustrates the critical role of N-glycosylation in guiding this recombinant enzyme replacement therapy’s delivery to the lysosomes.

Understanding Hunter Syndrome

Hunter syndrome is a rare genetic disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. This mutation results in a deficiency of the IDS enzyme, which is necessary for breaking down glycosaminoglycans (GAGs). In patients with this condition, GAGs accumulate within lysosomes, leading to serious symptoms such as physical and mental impairment, and ultimately, a decreased quality of life. Effective treatment hinges on the successful delivery of therapeutic enzymes to the lysosomes to promote the breakdown of these harmful accumulations.

Mechanism of Delivery

The recent study identified the necessity of specific N-glycan structures containing mannose-6-phosphate (M6P) for effective lysosomal targeting by the therapeutic enzyme. M6P serves as a signaling marker, facilitating the binding of the enzyme to target cells, promoting its uptake and subsequent delivery to lysosomes for GAG degradation.

Using high-resolution Orbitrap mass spectrometry, researchers successfully mapped 42 different N-glycan structures associated with idursulfase beta. Remarkably, they found that two specific sites, Asn221 and Asn255, were heavily modified with bis-mannose-6-phosphate (bis-M6P), which possesses two phosphate groups vital for achieving efficient delivery to lysosomes.

The study further demonstrated the strong binding affinity of idursulfase beta to M6P receptors utilizing surface plasmon resonance techniques. Confirmation of effective enzyme uptake and delivery was achieved through fluorescence-labeled cellular studies, underlining the robustness of these findings.

Additionally, noted was the presence of several N-glycan structures of idursulfase beta modified with sialic acid. This modification is essential as it extends the enzyme's circulation time within the bloodstream, thus prolonging its therapeutic half-life and effectiveness.

Conclusion

GC Biopharma emphasized that Hunterase is a highly effective therapy for Hunter syndrome, owing largely to its precise lysosomal delivery system, which is fundamentally driven by N-glycan structures endowed with M6P. Furthermore, sialic acid modifications play a significant role in prolonging circulation, enhancing patient treatment outcomes.

Dr. Jae Uk Jeong, Head of R&D at GC Biopharma, expressed confidence in the study’s findings, stating, “This study analyzed the lysosomal delivery mechanism of Hunterase, supported by robust scientific evidence. With clear evidence of its therapeutic effectiveness, patients with Hunter syndrome can have greater confidence in using Hunterase throughout their treatment journey.”

About GC Biopharma

GC Biopharma, previously known as Green Cross Corporation, is situated in Yongin, South Korea, and boasts over 50 years of expertise in developing and manufacturing plasma derivatives and vaccines. The company is actively seeking to expand its global footprint, marked by the successful introduction of its product Alyglo® in the U.S. market in 2024. GC Biopharma intends to continue pushing the boundaries of innovation in healthcare, particularly in the realm of rare diseases and immunology.

For further details, you can visit GC Biopharma's official website.