PDF(Pubmed)
Abstract：
Fragile X (FMR1) premutation is a common mutation that affects about 1 in 200 females and 1 in 450 males and can lead to the development of fragile-X-associated tremor/ataxia syndrome (FXTAS). Although there is no targeted, proven treatment for FXTAS, research suggests that sulforaphane, an antioxidant present in cruciferous vegetables, can enhance mitochondrial function and maintain redox balance in the dermal fibroblasts of individuals with FXTAS, potentially leading to improved cognitive function. In a 24-week open-label trial involving 15 adults aged 60-88 with FXTAS, 11 participants successfully completed the study, demonstrating the safety and tolerability of sulforaphane. Clinical outcomes and biomarkers were measured to elucidate the effects of sulforaphane. While there were nominal improvements in multiple clinical measures, they were not significantly different after correction for multiple comparisons. PBMC energetic measures showed that the level of citrate synthase was higher after sulforaphane treatment, resulting in lower ATP production. The ratio of complex I to complex II showed positive correlations with the MoCA and BDS scores. Several mitochondrial biomarkers showed increased activity and quantity and were correlated with clinical improvements.
摘要：
脆性X（FMR1）前突变是一种常见的突变，影响约200名女性中的1名和450名男性中的1名，并可导致脆性X相关的震颤/共济失调综合征（FXTAS）的发展。虽然没有针对性,对FXTAS的有效治疗，研究表明萝卜硫素,十字花科蔬菜中存在的抗氧化剂，可以增强线粒体功能并维持FXTAS患者皮肤成纤维细胞的氧化还原平衡，可能导致认知功能的改善。在一项为期24周的开放标签试验中，15名年龄在60-88岁的成年人患有FXTAS，11名参与者成功完成研究，证明萝卜硫素的安全性和耐受性。测量临床结果和生物标志物以阐明萝卜硫素的作用。虽然多项临床措施都有名义上的改善，经多重比较校正后,两者无显著差异.PBMC能量测量显示，萝卜硫烷处理后柠檬酸合成酶水平较高，导致较低的ATP产量。复合物I与复合物II的比率与MoCA和BDS评分呈正相关。几种线粒体生物标志物显示活性和数量增加，并与临床改善相关。
