Genome sequencing is often pivotal in the diagnosis of rare diseases, but many of these conditions lack specific treatments. We describe how molecular diagnosis of a rare, fatal neurodegenerative condition led to the rational design, testing, and manufacture of milasen, a splice-modulating antisense oligonucleotide drug tailored to a particular patient. Proof-of-concept experiments in cell lines from the patient served as the basis for launching an "N-of-1" study of milasen within 1 year after first contact with the patient. There were no serious adverse events, and treatment was associated with objective reduction in seizures (determined by electroencephalography and parental reporting). This study offers a possible template for the rapid development of patient-customized treatments. (Funded by Mila's Miracle Foundation and others.).

中文翻译：

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针对罕见遗传病的患者定制寡核苷酸疗法。

基因组测序通常是罕见病诊断的关键，但是许多这种疾病缺乏特定的治疗方法。我们描述了罕见的，致命的神经退行性疾病的分子诊断如何导致合理设计，测试和制造milasen（一种针对特定患者的剪接调节反义寡核苷酸药物）的合理设计。来自患者的细胞系中的概念验证实验，是在首次与患者接触后1年之内开展“ milasen”研究的“ N-of-1”研究的基础。没有严重的不良事件，并且治疗与癫痫发作的客观减少有关（由脑电图和父母报告确定）。这项研究为快速开发患者定制治疗方法提供了可能的模板。（由Mila的奇迹基金会和其他机构资助。）