Fabry Disease Therapy: State-of-the-Art and Current Challenges
Abstract
:1. Fabry Disease Overview
2. ERT
2.1. Efficacy and Safety of ERT
2.2. Best Timing to Start ERT
2.3. Optimal Dose of ERT
2.3.1. Agalsidase Alfa vs. Agalsidase Beta at Licensed Dose
2.3.2. Agalsidase Beta at Reduced Dose
2.3.3. Switch between Therapies
2.3.4. Agalsidase Alfa at Increased Dose
2.4. Limitations of ERT
2.4.1. Limited Tissue Penetration
2.4.2. No Crossing of the Blood-Brain Barrier
2.4.3. Infusion-Associated Reactions
2.4.4. Anti-Drug Antibodies
3. Migalastat
3.1. Efficacy and Safety of Migalastat
3.2. “In Vitro” and “In Vivo” Amenability to Migalastat
3.3. Limitations and Potential Advantages of Migalastat
3.4. Emerging New FD Therapies
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Agalsidase Alfa | Agalsidase Beta | Migalastat | |
---|---|---|---|
Definition | Recombinant α-galactosidase A produced from human fibroblasts [11] | Recombinant α-galactosidase A produced from Chinese hamster ovary (CHO) cells [11] | Low molecular weight iminosugar analogue of the terminal galactose residue of GB3 [42,43,44] |
Mechanism of action | Enzyme replacement therapy [11] | Enzyme replacement therapy [11] | Pharmacological chaperone that selectively and reversibly binds to the active site of amenable mutant forms of α-galactosidase A, stabilizing it, preventing its retention in the ER, and enabling its trafficking to the lysosomes [42,43,44] |
Administration route | Intravenous [45] | Intravenous [46] | Oral [47] |
Dose and frequency of administration | 0.2 mg/Kg every other week [45] | 1 mg/Kg every other week [46] | 123 mg once every other day [47] |
Efficacy | Males
| Males
Females |
|
Safety |
|
Advantages | Limitations | |
---|---|---|
ERT |
|
|
Migalastat |
|
|
Potential Advantages | Potential Limitations | |
---|---|---|
Pegunigalsidase alfa |
| |
Moss-derived α-galactosidase A |
| |
Substrate reduction therapy | ||
mRNA therapy | ||
Gene therapy |
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Azevedo, O.; Gago, M.F.; Miltenberger-Miltenyi, G.; Sousa, N.; Cunha, D. Fabry Disease Therapy: State-of-the-Art and Current Challenges. Int. J. Mol. Sci. 2021, 22, 206. https://doi.org/10.3390/ijms22010206
Azevedo O, Gago MF, Miltenberger-Miltenyi G, Sousa N, Cunha D. Fabry Disease Therapy: State-of-the-Art and Current Challenges. International Journal of Molecular Sciences. 2021; 22(1):206. https://doi.org/10.3390/ijms22010206
Chicago/Turabian StyleAzevedo, Olga, Miguel Fernandes Gago, Gabriel Miltenberger-Miltenyi, Nuno Sousa, and Damião Cunha. 2021. "Fabry Disease Therapy: State-of-the-Art and Current Challenges" International Journal of Molecular Sciences 22, no. 1: 206. https://doi.org/10.3390/ijms22010206
APA StyleAzevedo, O., Gago, M. F., Miltenberger-Miltenyi, G., Sousa, N., & Cunha, D. (2021). Fabry Disease Therapy: State-of-the-Art and Current Challenges. International Journal of Molecular Sciences, 22(1), 206. https://doi.org/10.3390/ijms22010206