Abstract:
:Lysosomal storage diseases (LSDs) are a group of genetic disorders due to defects in any aspect of lysosomal biology. During the past two decades, different approaches have been introduced for the treatment of these conditions. Among them, enzyme replacement therapy (ERT) represented a major advance and is used successfully in the treatment of some of these disorders. However, ERT has limitations such as insufficient biodistribution of recombinant enzymes and high costs. An emerging strategy for the treatment of LSDs is pharmacological chaperone therapy (PCT), based on the use of chaperone molecules that assist the folding of mutated enzymes and improve their stability and lysosomal trafficking. After proof-of-concept studies, PCT is now being translated into clinical applications for Fabry, Gaucher and Pompe disease. This approach, however, can only be applied to patients carrying chaperone-responsive mutations. The recent demonstration of a synergistic effect of chaperones and ERT expands the applications of PCT and prompts a re-evaluation of their therapeutic use and potential. This review discusses the strengths and drawbacks of the potential therapies available for LSDs and proposes that future research should be directed towards the development of treatment protocols based on the combination of different therapies to improve the clinical outcome of LSD patients.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Parenti Gdoi
10.1002/emmm.200900036subject
Has Abstractpub_date
2009-08-01 00:00:00pages
268-79issue
5eissn
1757-4676issn
1757-4684journal_volume
1pub_type
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