Laboratório de Células, Tecidos e Genes - Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, UFRGS, Porto Alegre, RS, Brazil.
Laboratório de Células, Tecidos e Genes - Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Genética e Biologia Molecular, UFRGS, Porto Alegre, RS, Brazil.
Adv Drug Deliv Rev. 2022 Dec;191:114616. doi: 10.1016/j.addr.2022.114616. Epub 2022 Nov 7.
Lysosomal storage disorders are a group of progressive multisystemic hereditary diseases with a combined incidence of 1:4,800. Here we review the clinical and molecular characteristics of these diseases, with a special focus on Mucopolysaccharidoses, caused primarily by the lysosomal storage of glycosaminoglycans. Different gene editing techniques can be used to ameliorate their symptoms, using both viral and nonviral delivery methods. Whereas these are still being tested in animal models, early results of phase I/II clinical trials of gene therapy show how this technology may impact the future treatment of these diseases. Hurdles related to specific hard-to-reach organs, such as the central nervous system, heart, joints, and the eye must be tackled. Finally, the regulatory framework necessary to advance into clinical practice is also discussed.
溶酶体贮积症是一组进行性多系统遗传性疾病,合并发病率为 1:4800。在这里,我们回顾了这些疾病的临床和分子特征,特别关注了粘多糖贮积症,其主要是由于溶酶体中糖胺聚糖的贮积引起的。不同的基因编辑技术可用于改善这些疾病的症状,包括病毒和非病毒传递方法。虽然这些方法仍在动物模型中进行测试,但基因治疗的 I/II 期临床试验的早期结果表明,这项技术可能会如何影响这些疾病的未来治疗。必须解决与特定难以到达的器官(如中枢神经系统、心脏、关节和眼睛)相关的障碍。最后,还讨论了推进临床实践所需的监管框架。