Preprint Review Version 1 This version is not peer-reviewed

Pharmacological Chaperones for the Mucopolysaccharidoses

Version 1 : Received: 30 October 2019 / Approved: 31 October 2019 / Online: 31 October 2019 (09:33:43 CET)

How to cite: Losada Diaz, J.C.; Cepeda Del Castillo, J.; Rodríguez López, E.A.; Alméciga-Díaz, C.J. Pharmacological Chaperones for the Mucopolysaccharidoses. Preprints 2019, 2019100365 (doi: 10.20944/preprints201910.0365.v1). Losada Diaz, J.C.; Cepeda Del Castillo, J.; Rodríguez López, E.A.; Alméciga-Díaz, C.J. Pharmacological Chaperones for the Mucopolysaccharidoses. Preprints 2019, 2019100365 (doi: 10.20944/preprints201910.0365.v1).

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.

Subject Areas

pharmacological chaperones; mucopolysaccharidoses; mps; small molecules

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