Fabry disease: Mechanism and therapeutics strategies
Fabry disease is a monogenic disease characterized by a deficiency or loss of the α-galactosidase A (GLA). The resulting impairment in lysosomal GLA enzymatic activity leads to the pathogenic accumulation of enzymatic substrate and, consequently, the progressive appearance of clinical symptoms in ta...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1025740/full |
| _version_ | 1798027533761904640 |
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| author | Xi Li Xiangyi Ren Yabing Zhang Lin Ding Minfeng Huo Qian Li |
| author_facet | Xi Li Xiangyi Ren Yabing Zhang Lin Ding Minfeng Huo Qian Li |
| author_sort | Xi Li |
| collection | DOAJ |
| description | Fabry disease is a monogenic disease characterized by a deficiency or loss of the α-galactosidase A (GLA). The resulting impairment in lysosomal GLA enzymatic activity leads to the pathogenic accumulation of enzymatic substrate and, consequently, the progressive appearance of clinical symptoms in target organs, including the heart, kidney, and brain. However, the mechanisms involved in Fabry disease-mediated organ damage are largely ambiguous and poorly understood, which hinders the development of therapeutic strategies for the treatment of this disorder. Although currently available clinical approaches have shown some efficiency in the treatment of Fabry disease, they all exhibit limitations that need to be overcome. In this review, we first introduce current mechanistic knowledge of Fabry disease and discuss potential therapeutic strategies for its treatment. We then systemically summarize and discuss advances in research on therapeutic approaches, including enzyme replacement therapy (ERT), gene therapy, and chaperone therapy, as well as strategies targeting subcellular compartments, such as lysosomes, the endoplasmic reticulum, and the nucleus. Finally, the future development of potential therapeutic strategies is discussed based on the results of mechanistic studies and the limitations associated with these therapeutic approaches. |
| first_indexed | 2024-04-11T18:53:19Z |
| format | Article |
| id | doaj.art-91712a715ce64e89b4684dbc725b4914 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T18:53:19Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-91712a715ce64e89b4684dbc725b49142022-12-22T04:08:17ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10257401025740Fabry disease: Mechanism and therapeutics strategiesXi Li0Xiangyi Ren1Yabing Zhang2Lin Ding3Minfeng Huo4Qian Li5Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, ChinaCore Facilities of West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Anesthesiology, West China Hospital of Sichuan University, Chengdu, ChinaDepartment of Anesthesiology, West China Hospital of Sichuan University, Chengdu, ChinaShanghai Tenth People’s Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Anesthesiology, West China Hospital of Sichuan University, Chengdu, ChinaFabry disease is a monogenic disease characterized by a deficiency or loss of the α-galactosidase A (GLA). The resulting impairment in lysosomal GLA enzymatic activity leads to the pathogenic accumulation of enzymatic substrate and, consequently, the progressive appearance of clinical symptoms in target organs, including the heart, kidney, and brain. However, the mechanisms involved in Fabry disease-mediated organ damage are largely ambiguous and poorly understood, which hinders the development of therapeutic strategies for the treatment of this disorder. Although currently available clinical approaches have shown some efficiency in the treatment of Fabry disease, they all exhibit limitations that need to be overcome. In this review, we first introduce current mechanistic knowledge of Fabry disease and discuss potential therapeutic strategies for its treatment. We then systemically summarize and discuss advances in research on therapeutic approaches, including enzyme replacement therapy (ERT), gene therapy, and chaperone therapy, as well as strategies targeting subcellular compartments, such as lysosomes, the endoplasmic reticulum, and the nucleus. Finally, the future development of potential therapeutic strategies is discussed based on the results of mechanistic studies and the limitations associated with these therapeutic approaches.https://www.frontiersin.org/articles/10.3389/fphar.2022.1025740/fullfabry diseaselysosomal storage disordermechanistic researchfabry therapeutic strategiesalpha-galactosidase A deficiency |
| spellingShingle | Xi Li Xiangyi Ren Yabing Zhang Lin Ding Minfeng Huo Qian Li Fabry disease: Mechanism and therapeutics strategies Frontiers in Pharmacology fabry disease lysosomal storage disorder mechanistic research fabry therapeutic strategies alpha-galactosidase A deficiency |
| title | Fabry disease: Mechanism and therapeutics strategies |
| title_full | Fabry disease: Mechanism and therapeutics strategies |
| title_fullStr | Fabry disease: Mechanism and therapeutics strategies |
| title_full_unstemmed | Fabry disease: Mechanism and therapeutics strategies |
| title_short | Fabry disease: Mechanism and therapeutics strategies |
| title_sort | fabry disease mechanism and therapeutics strategies |
| topic | fabry disease lysosomal storage disorder mechanistic research fabry therapeutic strategies alpha-galactosidase A deficiency |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1025740/full |
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