PDF(Pubmed)
Abstract：
Fluoxetine has been identified as a potential treatment for mucopolysaccharidosis IIIA (MPS IIIA), a debilitating and progressive lysosomal storage disorder for which no treatments are approved. In the MPS IIIA mouse model, fluoxetine decreases the accumulation of glycosaminoglycans and aggregated autophagic substrates, reducing inflammation, and slowing cognitive deterioration. 1 We treated a single patient, 6 years old, under off-label prescription of fluoxetine, a selective serotonin reuptake inhibitor (SSRI). The primary endpoint was safety. Secondary exploratory assessments included urine quantitative heparan sulfate. Fluoxetine was well-tolerated in this patient and the patient continued treatment following the 12-month monitoring period. The patient experienced an increase in daytime somnolence which resolved with rescheduling fluoxetine administration to bedtime. Quantitative heparan sulfate levels remained elevated during treatment. Parents reported improved sleep latency time and less nighttime waking. These findings support general tolerability and further study of fluoxetine as a potential therapy for MPS IIIA.
摘要：
氟西汀已被确定为粘多糖贮积症IIIA（MPSIIIA）的潜在治疗方法，一种衰弱性和进行性溶酶体贮积症，没有批准治疗。在MPSIIIA小鼠模型中，氟西汀减少糖胺聚糖和聚集的自噬底物的积累，减少炎症，和减缓认知退化。1我们治疗了一个病人，6岁,氟西汀的超标签处方，选择性5-羟色胺再摄取抑制剂(SSRI)。主要终点是安全性。二次探索性评估包括尿定量硫酸乙酰肝素。氟西汀在该患者中具有良好的耐受性,并且患者在12个月的监测期后继续治疗。患者经历了白天嗜睡的增加，通过将氟西汀的给药改期至就寝时间来解决。定量硫酸乙酰肝素水平在治疗期间保持升高。父母报告睡眠潜伏期改善，夜间清醒时间减少。这些发现支持氟西汀作为MPSIIIA潜在疗法的一般耐受性和进一步研究。
