Mucopolysaccharidosis type IIIB (MPS IIIB) is a lysosomal disease caused by mutations in the NAGLU gene encoding α-N-acetylglucosaminidase (NAGLU) which degrades heparan sulfate in lysosomes. Deficiency in NAGLU results in lysosomal accumulation of glycosaminoglycans (GAGs) and neurological symptoms. Currently, there is no effective treatment or cure for this disease. In this study, induced pluripotent stem cell lines were established from two MPS IIIB patient fibroblast lines and differentiated into neural stem cells and neurons. MPS IIIB neural stem cells exhibited NAGLU deficiency accompanied with GAG accumulation, as well as lysosomal enlargement and secondary lipid accumulation. Treatments with recombinant NAGLU, δ-tocopherol, and 2-hydroxypropyl-b-cyclodextrin significantly reduced the disease phenotypes in these cells. These results indicate the MPS IIIB neural stem cells and neurons have the disease relevant phenotype and can be used as a cell-based disease model system for evaluation of drug efficacy and compound screening for drug development.

IIIB 型粘多糖贮积症 (MPS IIIB) 是一种由NAGLU突变引起的溶酶体疾病编码α-N-乙酰氨基葡萄糖苷酶（NAGLU）的基因，可降解溶酶体中的硫酸乙酰肝素。NAGLU 缺乏会导致糖胺聚糖 (GAG) 的溶酶体积累和神经系统症状。目前，这种疾病没有有效的治疗方法或治愈方法。在这项研究中，诱导多能干细胞系由两个 MPS IIIB 患者成纤维细胞系建立，并分化为神经干细胞和神经元。MPS IIIB 神经干细胞表现出 NAGLU 缺乏并伴有 GAG 积累，以及溶酶体增大和继发性脂质积累。用重组 NAGLU、δ-生育酚和 2-羟丙基-b-环糊精治疗显着降低了这些细胞中的疾病表型。