Losada Díaz, J.C.; Cepeda del Castillo, J.; Rodriguez-López, E.A.; Alméciga-Díaz, C.J. Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses. Int. J. Mol. Sci.2020, 21, 232.
Losada Díaz, J.C.; Cepeda del Castillo, J.; Rodriguez-López, E.A.; Alméciga-Díaz, C.J. Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses. Int. J. Mol. Sci. 2020, 21, 232.
Losada Díaz, J.C.; Cepeda del Castillo, J.; Rodriguez-López, E.A.; Alméciga-Díaz, C.J. Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses. Int. J. Mol. Sci.2020, 21, 232.
Losada Díaz, J.C.; Cepeda del Castillo, J.; Rodriguez-López, E.A.; Alméciga-Díaz, C.J. Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses. Int. J. Mol. Sci. 2020, 21, 232.
Abstract
The mucopolysaccharidoses (MPS) are a group of 11 lysosomal storage diseases (LSDs) produced by mutations in the enzymes involved in the lysosomal catabolism of glycosaminoglycans. Most of the mutations affecting these enzymes may lead to changes in processing, folding, glycosylation, pH stability, protein aggregation, and defective transport to the lysosomes. The use of small molecules, called pharmacological chaperones (PCs), that can restore the folding, trafficking and biological activity of mutated enzymes has been extensively explored in LSDs as a therapeutic alternative. PCs have the advantage of wide tissue distribution, potential oral administration, lower production cost, and fewer issues of immunogenicity. In this paper, we will review the advances in the identification and characterization of PCs for the MPS. These molecules, mainly based in molecules mimicking the enzyme substrates, have been described for MPS II, IVA, and IVB, showing a mutation-dependent enhancement of the mutated enzymes. Although the results show the potential of this strategy, further studies should focus in the development of disease-specific cellular models that allow a proper screening and evaluation of the identified PCs. In addition, in vivo evaluation, both pre-clinical and clinical, should be performed, before they can become a real therapeutic strategy for the treatment of MPS patients.
Keywords
pharmacological chaperones; mucopolysaccharidoses; mps; small molecules
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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