Stop-codon read-through for patients affected by a lysosomal storage disorder.
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.
Brooks
Doug A
DA
Lysosomal Diseases Research Unit, Department of Genetic Medicine, Children Youth and Women's Health Service, 72 King William Rd, North Adelaide, South Australia 5006, Australia. douglas.brooks@adelaide.edu.au
Muller
Viv J
VJ
Hopwood
John J
JJ
D018389:Codon, Nonsense / Q000235:genetics; D018388:Codon, Terminator / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D005839:Gentamicins / Q000627:therapeutic use; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000188:drug therapy / Q000235:genetics*; D008954:Models, Biological
D018389:Codon, Nonsense; D018388:Codon, Terminator; D005839:Gentamicins