The aim of this study was to evaluate the efficacy of high dose genistein aglycone in Sanfilippo syndrome (mucopolysaccharidosis type III). High doses of genistein aglycone have been shown to correct neuropathology and hyperactive behaviour in mice, but efficacy in humans is uncertain. This was a single centre, double-blinded, randomised, placebo-controlled study with open-label extension phase. Randomised participants received either 160 mg/kg/day genistein aglycone or placebo for 12 months; subsequently all participants received genistein for 12 months. The primary outcome measure was the change in heparan sulfate concentration in cerebrospinal fluid (CSF), with secondary outcome measures including heparan sulfate in plasma and urine, total glycosaminoglycans in urine, cognitive and adaptive behaviour scores, quality of life measures and actigraphy. Twenty-one participants were randomised and 20 completed the placebo-controlled phase. After 12 months of treatment, the CSF heparan sulfate concentration was 5.5% lower in the genistein group (adjusted for baseline values), but this was not statistically significant (P = .26), and CSF heparan sulfate increased in both groups during the open-label extension phase. Reduction of urinary glycosaminoglycans was significantly greater in the genistein group (32.1% lower than placebo after 12 months, P = .0495). Other biochemical and clinical parameters showed no significant differences between groups. High dose genistein aglycone (160 mg/kg/day) was not associated with clinically meaningful reductions in CSF heparan sulfate and no evidence of clinical efficacy was detected. However, there was a statistically significant reduction in urine glycosaminoglycans. These data do not support the use of genistein aglycone therapy in mucopolysaccharidosis type III. High dose genistein aglycone does not lead to clinically meaningful reductions in biomarkers or improvement in neuropsychological outcomes in mucopolysaccharidosis type III.

中文翻译：

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高剂量染料木黄酮治疗 Sanfilippo 综合征：一项随机对照试验

本研究的目的是评估高剂量染料木素苷元在 Sanfilippo 综合征（粘多糖贮积症 III 型）中的疗效。高剂量的染料木黄酮糖苷配基已被证明可以纠正小鼠的神经病理学和多动行为，但对人类的疗效尚不确定。这是一项单中心、双盲、随机、安慰剂对照研究，具有开放标签扩展阶段。随机参与者接受 160 mg/kg/天的染料木黄酮糖苷配基或安慰剂，持续 12 个月；随后，所有参与者都接受了 12 个月的染料木黄酮。主要结果指标是脑脊液 (CSF) 中硫酸乙酰肝素浓度的变化，次要结果指标包括血浆和尿液中的硫酸乙酰肝素、尿液中的总糖胺聚糖、认知和适应行为评分、生活质量测量和活动记录。21 名参与者被随机分配，20 名参与者完成了安慰剂对照阶段。治疗 12 个月后，染料木黄酮组的 CSF 硫酸乙酰肝素浓度降低了 5.5%（针对基线值进行了调整），但这在统计学上并不显着（P  = .26)，并且在开放标签延伸阶段，两组的 CSF 硫酸乙酰肝素均增加。染料木黄酮组尿液糖胺聚糖的减少明显更多（12 个月后比安慰剂低 32.1%，P =.0495）。其他生化和临床参数显示组间无显着差异。高剂量染料木黄酮糖苷配基 (160 mg/kg/day) 与具有临床意义的 CSF 硫酸乙酰肝素减少无关，也未检测到临床疗效的证据。然而，尿糖胺聚糖在统计学上有显着减少。这些数据不支持在 III 型粘多糖贮积症中使用染料木素苷元疗法。高剂量染料木黄酮糖苷配基不会导致具有临床意义的生物标志物减少或 III 型粘多糖贮积症神经心理学结果的改善。