Mucopolysaccharidosis IIIB (MPS IIIB, Sanfilippo syndrome type B) is caused by a deficiency in α-N-acetylglucosaminidase (NAGLU) activity, which leads to the accumulation of heparan sulfate (HS). MPS IIIB causes progressive neurological decline, with affected patients having an expected lifespan of approximately 20 years. No effective treatment is available. Recent pre-clinical studies have shown that intracerebroventricular (ICV) ERT with a fusion protein of rhNAGLU-IGF2 is a feasible treatment for MPS IIIB in both canine and mouse models. In this study, we evaluated the biochemical efficacy of a single dose of rhNAGLU-IGF2 via ICV-ERT in brain and liver tissue from Naglu^−/− neonatal mice. Twelve weeks after treatment, NAGLU activity levels in brain were 0.75-fold those of controls. HS and β-hexosaminidase activity, which are elevated in MPS IIIB, decreased to normal levels. This effect persisted for at least 4 weeks after treatment. Elevated NAGLU and reduced β-hexosaminidase activity levels were detected in liver; these effects persisted for up to 4 weeks after treatment. The overall therapeutic effects of single dose ICV-ERT with rhNAGLU-IGF2 in Naglu^−/− neonatal mice were long-lasting. These results suggest a potential benefit of early treatment, followed by less-frequent ICV-ERT dosing, in patients diagnosed with MPS IIIB.

粘多糖贮积症 IIIB（MPS IIIB，Sanfilippo 综合征 B 型）是由 α - N-乙酰氨基葡萄糖苷酶 (NAGLU) 活性不足引起的，这会导致硫酸乙酰肝素 (HS) 的积累。MPS IIIB 会导致进行性神经功能衰退，受影响的患者的预期寿命约为 20 年。没有有效的治疗方法。最近的临床前研究表明，在犬和小鼠模型中，使用 rhNAGLU-IGF2 融合蛋白的脑室内 (ICV) ERT 是治疗 MPS IIIB 的可行方法。在这项研究中，我们通过 ICV-ERT 评估了单剂量 rhNAGLU-IGF2 在 Naglu 的脑和肝组织中的生化功效- ^/-新生小鼠。治疗 12 周后，大脑中的 NAGLU 活性水平是对照组的 0.75 倍。MPS IIIB 中升高的 HS 和 β-氨基己糖苷酶活性降低至正常水平。这种效果在治疗后至少持续了 4 周。在肝脏中检测到 NAGLU 升高和 β-己糖胺酶活性水平降低；这些影响在治疗后持续长达 4 周。单剂量 ICV-ERT 与 rhNAGLU-IGF2 在Naglu ^-/-新生小鼠中的整体治疗效果是持久的。这些结果表明，在诊断为 MPS IIIB 的患者中，早期治疗的潜在益处，其次是较少频率的 ICV-ERT 给药。