Fabry disease (FD) is a progressive multisystemic disease characterized by lysosomal enzyme deficiency. Enzyme replacement therapy (ERT) is one of the most significant advancements and breakthroughs in treating FD. However, limited resources and the high cost of ERT might prevent patients from receiving prompt and effective therapy, thereby resulting in severe complications. Future progress in ERT can uncover promising treatment options. In this study, we developed and validated a recombinant enzyme (Lanzyme) based on a CHO-S cell system to provide a new potential option for FD therapy. Our results indicated that Lanzyme was heavily glycosylated, and its highest activity was similar to a commercial enzyme (Fabrazyme®). Our pharmacokinetic assessment revealed that the half-life of Lanzyme was up to 11 min, which is nearly twice that of the commercial enzyme. In vivo experiments revealed that Lanzyme treatment sharply decreased the accumulation levels of Gb3 and lyso-Gb3 in various tissues of FD model mice, with superior or comparable therapeutic effects to Fabrazyme®. Based on these data, Lanzyme may represent a new and promising treatment approach for FD. Building this enzyme production system for ERT can offer additional choice, potentially with enhanced efficacy, for the benefit of patients with FD.
Keywords: Fabry disease (FD); Lanzyme; enzyme replacement therapy (ERT); globotriaosylceramide (Gb3); lysosomal storage disorders (LSDs); recombinant human α-galactosidase A (rhα-Gal A).