Development of Lanzyme as the Potential Enzyme Replacement Therapy Drug for Fabry Disease
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 recei...
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MDPI AG
2022-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/1/53 |
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| author | Mulan Deng Hongyu Zhou Zhicheng Liang Zhaoyang Li Yanping Wang Wanyi Guo April Yuanyi Zhao Fanghong Li Yunping Mu Allan Zijian Zhao |
| author_facet | Mulan Deng Hongyu Zhou Zhicheng Liang Zhaoyang Li Yanping Wang Wanyi Guo April Yuanyi Zhao Fanghong Li Yunping Mu Allan Zijian Zhao |
| author_sort | Mulan Deng |
| collection | DOAJ |
| description | 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<sup>®</sup>). 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<sup>®</sup>. 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. |
| first_indexed | 2024-03-09T13:27:15Z |
| format | Article |
| id | doaj.art-65a733ff7de84060b59c4e97f0c1b379 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T13:27:15Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-65a733ff7de84060b59c4e97f0c1b3792023-11-30T21:22:04ZengMDPI AGBiomolecules2218-273X2022-12-011315310.3390/biom13010053Development of Lanzyme as the Potential Enzyme Replacement Therapy Drug for Fabry DiseaseMulan Deng0Hongyu Zhou1Zhicheng Liang2Zhaoyang Li3Yanping Wang4Wanyi Guo5April Yuanyi Zhao6Fanghong Li7Yunping Mu8Allan Zijian Zhao9The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510000, ChinaThe School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510000, ChinaThe School of Medicine, South China University of Technology, Guangzhou 510000, ChinaThe School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510000, ChinaThe School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510000, ChinaThe School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510000, ChinaThe School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510000, ChinaThe School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510000, ChinaThe School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510000, ChinaThe School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510000, ChinaFabry 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<sup>®</sup>). 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<sup>®</sup>. 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.https://www.mdpi.com/2218-273X/13/1/53lysosomal storage disorders (LSDs)recombinant human α-galactosidase A (rhα-Gal A)Fabry disease (FD)enzyme replacement therapy (ERT)globotriaosylceramide (Gb3)Lanzyme |
| spellingShingle | Mulan Deng Hongyu Zhou Zhicheng Liang Zhaoyang Li Yanping Wang Wanyi Guo April Yuanyi Zhao Fanghong Li Yunping Mu Allan Zijian Zhao Development of Lanzyme as the Potential Enzyme Replacement Therapy Drug for Fabry Disease Biomolecules lysosomal storage disorders (LSDs) recombinant human α-galactosidase A (rhα-Gal A) Fabry disease (FD) enzyme replacement therapy (ERT) globotriaosylceramide (Gb3) Lanzyme |
| title | Development of Lanzyme as the Potential Enzyme Replacement Therapy Drug for Fabry Disease |
| title_full | Development of Lanzyme as the Potential Enzyme Replacement Therapy Drug for Fabry Disease |
| title_fullStr | Development of Lanzyme as the Potential Enzyme Replacement Therapy Drug for Fabry Disease |
| title_full_unstemmed | Development of Lanzyme as the Potential Enzyme Replacement Therapy Drug for Fabry Disease |
| title_short | Development of Lanzyme as the Potential Enzyme Replacement Therapy Drug for Fabry Disease |
| title_sort | development of lanzyme as the potential enzyme replacement therapy drug for fabry disease |
| topic | lysosomal storage disorders (LSDs) recombinant human α-galactosidase A (rhα-Gal A) Fabry disease (FD) enzyme replacement therapy (ERT) globotriaosylceramide (Gb3) Lanzyme |
| url | https://www.mdpi.com/2218-273X/13/1/53 |
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