Development of trofinetide for the treatment of Rett syndrome: from bench to bedside
Development of trofinetide for the treatment of Rett syndrome: from bench to bedside
复制标题
用于治疗 Rett 综合征的曲芬肽的开发：从实验室到临床
DOI：
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发表时间：
2024
影响因子：
5.6
通讯作者：
James M. Youakim
中科院分区：
文献类型：
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作者：
Melissa Kennedy;L. Glass;D. Glaze;Steve Kaminsky;Alan K. Percy;J. Neul;Nancy E. Jones;Daniela Tropea;Joseph P. Horrigan;Paige Nues;Kathie M. Bishop;James M. Youakim
Rett综合征（RTT）是一种罕见的神经发育障碍，由编码甲基CpG结合蛋白2（MeCP 2）的MECP 2基因突变引起，MeCP 2是一种DNA结合蛋白，在基因表达的表观遗传调控中发挥作用。MeCP 2的功能丧失导致异常的神经元成熟和可塑性，其特征在于言语交流的丧失以及精细和粗大运动功能的丧失等。Trofinetide是甘氨酸-脯氨酸-谷氨酸盐的合成类似物，已被美国食品药品监督管理局批准用于治疗2岁及以上成人和儿童患者的RTT。在这里，我们介绍了trofinetide从实验室研究到临床研究的发展，并强调学术界，制药业和患者倡导之间的合作如何导致最近的批准。trofinetide的临床开发强调了这些小组之间在罕见疾病治疗的开发和批准方面的合作价值。
Rett syndrome (RTT) is rare neurodevelopmental disorder caused by mutations in the MECP2 gene that encodes methyl-CpG-binding protein 2 (MeCP2), a DNA-binding protein with roles in epigenetic regulation of gene expression. Functional loss of MeCP2 results in abnormal neuronal maturation and plasticity, characterized by loss of verbal communication and loss of fine and gross motor function, among others. Trofinetide, a synthetic analog of glycine-proline-glutamate, was approved by the US Food and Drug Administration for the treatment of RTT in adult and pediatric patients aged 2 years and older. Here, we present the development of trofinetide from bench research to clinical studies and emphasize how the collaboration between academia, the pharmaceutical industry, and patient advocacy led to the recent approval. The bench-to-bedside development of trofinetide underscores the value of collaboration between these groups in the development and approval of treatments for rare diseases.