Fragile X syndrome (FXS) is the most common form of intellectual disability and autism spectrum disorder and is caused by CGG repeat expansion in the promoter region of the FMR1 gene, which encodes fragile X mental retardation protein. This event leads to gene silencing and the loss of gene products through DNA methylation and chromatin remodeling. Due to the pathogenesis of FXS, targeted, symptomatic, and etiological approaches have been developed for its treatment. Despite their rapid development, symptomatic and targeted treatment approaches have numerous limitations; etiological approaches have the greatest potential because they affect the main causes of transcriptional silencing. In this review, we consider three potential etiological therapeutic methods that affect the reactivation of FMR1 gene expression: treatment with inhibitors of chromatin-modifying enzymes, the use of noncoding RNAs and the application of gene therapy. Inhibitors of chromatin-modifying enzymes are not clinically applicable because of their low reactivity and high cytotoxicity, and noncoding RNAs are currently only under study. Thus, we discuss gene therapy as the most promising approach for treating FXS in the near future.

脆性 X 综合征 (FXS) 是智力残疾和自闭症谱系障碍的最常见形式，由FMR1基因启动子区的 CGG 重复扩增引起，该基因编码脆性 X 智力低下蛋白。该事件通过 DNA 甲基化和染色质重塑导致基因沉默和基因产物的丢失。由于 FXS 的发病机制，已经开发了针对其治疗的靶向、对症和病因学方法。尽管发展迅速，但对症和靶向治疗方法仍有许多局限性。病因学方法具有最大的潜力，因为它们影响转录沉默的主要原因。在这篇综述中，我们考虑了影响FMR1重新激活的三种潜在病因治疗方法基因表达：染色质修饰酶抑制剂治疗、非编码RNA的使用和基因治疗的应用。染色质修饰酶抑制剂因其反应性低、细胞毒性高而不适用于临床，非编码 RNA 目前仅处于研究阶段。因此，我们将基因疗法作为在不久的将来治疗 FXS 的最有希望的方法进行讨论。