Brooks Doug A, Muller Viv J, Hopwood John J
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.
Trends Mol Med. 2006 Aug;12(8):367-73. doi: 10.1016/j.molmed.2006.06.001. Epub 2006 Jun 23.
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.
溶酶体贮积症是一组遗传性疾病，由于特定的溶酶体功能障碍，可导致严重且进行性的病理变化。目前的治疗策略包括骨髓移植、底物减少、化学伴侣和酶替代疗法。然而，这些治疗方法都有其局限性。增强的终止密码子通读是治疗溶酶体贮积症患者的一种潜在替代或辅助治疗策略。在一大群溶酶体贮积症患者中已鉴定出过早的终止密码子突变，这使得终止密码子通读成为这种疾病的一种可能治疗方法。在溶酶体贮积症细胞（I型黏多糖贮积症，α-L-艾杜糖醛酸酶缺陷）中，临床前研究表明庆大霉素可诱导过早终止密码子的通读，从而产生降低底物储存的酶活性。
