Less Is More: Substrate Reduction Therapy for Lysosomal Storage Disorders

Coutinho, Maria; Santos, Juliana; Alves, Sandra

http://hdl.handle.net/10400.18/4287

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Authors

Coutinho, Maria

Santos, Juliana

Alves, Sandra

Abstract(s)

Lysosomal storage diseases (LSDs) are a group of rare, life-threatening genetic disorders, usually caused by a dysfunction in one of the many enzymes responsible for intralysosomal digestion. Even though no cure is available for any LSD, a few treatment strategies do exist. Traditionally, efforts have been mainly targeting the functional loss of the enzyme, by injection of a recombinant formulation, in a process called enzyme replacement therapy (ERT), with no impact on neuropathology. This ineffectiveness, together with its high cost and lifelong dependence is amongst the main reasons why additional therapeutic approaches are being (and have to be) investigated: chaperone therapy; gene enhancement; gene therapy; and, alternatively, substrate reduction therapy (SRT), whose aim is to prevent storage not by correcting the original enzymatic defect but, instead, by decreasing the levels of biosynthesis of the accumulating substrate(s). Here we review the concept of substrate reduction, highlighting the major breakthroughs in the field and discussing the future of SRT, not only as a monotherapy but also, especially, as complementary approach for LSDs.

Description

This article has been corrected in: Coutinho et al. Less Is More: Substrate Reduction Therapy for Lysosomal Storage Disorders. Int. J. Mol. Sci. 2016, 17, 1065. Int. J. Mol. Sci. 2016, 17, 1065. Int J Mol Sci. 2017 Jan 17;18(1). pii: E178. doi: 10.3390/ijms18010178. Disponível em: http://www.mdpi.com/1422-0067/18/1/178

Keywords

Substrate Reduction Therapy (SRT) Miglustat Eeligluistat Tartrate Genistein Gaucher Disease (GD) Niemann-Pick Type C (NPC) Mucopolysaccharidosis Type III (MPS III; Sanfilippo Syndrome) combination Therapy Doenças Genéticas