Stop-codon read-through for patients affected by a lysosomal storage disorder

Trends Mol Med. 2006 Aug;12(8):367-73. doi: 10.1016/j.molmed.2006.06.001. Epub 2006 Jun 23.

Abstract

Lysosomal storage disorders are a group of inherited diseases that can result in severe and progressive pathology due to a specific lysosomal dysfunction. Current treatment strategies include bone-marrow transplantation, substrate reduction, chemical-chaperone and enzyme-replacement therapy. However, each of these treatments has its limitations. Enhanced stop-codon read-through is a potential alternative or adjunct therapeutic strategy for treating lysosomal-storage-disorder patients. Premature stop-codon mutations have been identified in a large cohort of patients with a lysosomal storage disorder, making stop-codon read-through a possible treatment for this disease. In lysosomal-storage-disorder cells (mucopolysaccharidosis type I, alpha-L-iduronidase deficient), preclinical studies have shown that gentamicin induced the read-through of premature stop codons, resulting in enzyme activity that reduced substrate storage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Codon, Nonsense / genetics
  • Codon, Terminator / genetics*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Gentamicins / therapeutic use
  • Humans
  • Lysosomal Storage Diseases / drug therapy
  • Lysosomal Storage Diseases / genetics*
  • Models, Biological

Substances

  • Codon, Nonsense
  • Codon, Terminator
  • Gentamicins