Next Article in Journal
Natural Bioactive Compounds: The Way Shown by Professor Maurizio Battino and His Group in an Italian Cutting-Edge Laboratory
Next Article in Special Issue
Practical Recommendations for Diagnosis and Management of Respiratory Muscle Weakness in Late-Onset Pompe Disease
Previous Article in Journal
Determination of Free-Form and Peptide Bound Pyrraline in the Commercial Drinks Enriched with Different Protein Hydrolysates
Previous Article in Special Issue
Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series
Article Menu
Issue 7 (July) cover image

Export Article

Correction published on 17 January 2017, see Int. J. Mol. Sci. 2017, 18(1), 178.

Open AccessReview
Int. J. Mol. Sci. 2016, 17(7), 1065; doi:10.3390/ijms17071065

Less Is More: Substrate Reduction Therapy for Lysosomal Storage Disorders

Department of Human Genetics, Research and Development Unit, National Health Institute Doutor Ricardo Jorge, Rua Alexandre Herculano, 321 4000-055 Porto, Portugal
*
Author to whom correspondence should be addressed.
Academic Editor: Ritva Tikkanen
Received: 27 May 2016 / Revised: 24 June 2016 / Accepted: 27 June 2016 / Published: 4 July 2016
View Full-Text   |   Download PDF [570 KB, uploaded 20 January 2017]   |  

Abstract

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. View Full-Text
Keywords: substrate reduction therapy (SRT); miglustat; eligluistat tartrate; genistein; Gaucher disease (GD); Niemann-Pick type C (NPC); mucopolysaccharidosis type III (MPS III; Sanfilippo syndrome); combination therapy substrate reduction therapy (SRT); miglustat; eligluistat tartrate; genistein; Gaucher disease (GD); Niemann-Pick type C (NPC); mucopolysaccharidosis type III (MPS III; Sanfilippo syndrome); combination therapy
Figures

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. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Coutinho, M.F.; Santos, J.I.; Alves, S. Less Is More: Substrate Reduction Therapy for Lysosomal Storage Disorders. Int. J. Mol. Sci. 2016, 17, 1065.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top