Intrathecal 2-hydroxypropyl-beta-cyclodextrin in a single patient with Niemann-Pick C1.
Intrathecal 2-hydroxypropyl-beta-cyclodextrin in a single patient with Niemann-Pick C1.
复制标题
DOI：
10.1016/j.ymgme.2015.07.001
复制
发表时间：
2015-09
影响因子：
3.8
通讯作者：
Dickson PI
中科院分区：
文献类型：
--
作者：
Maarup TJ;Chen AH;Porter FD;Farhat NY;Ory DS;Sidhu R;Jiang X;Dickson PI
尼曼-匹克C型1型（NPC 1）是一种进行性常染色体隐性遗传神经系统疾病，由细胞内胆固醇和脂质转运缺陷引起。目前没有美国食品和药物管理局批准的NPC 1治疗方法。我们开展了一项研究，评价鞘内注射2-羟丙基-β-环糊精（HP-β-CD）在1例12岁轻度症状性NPC受试者中的安全性、疗效和生物标志物反应。该受试者通过腰椎穿刺鞘内注射HP-β-CD 200 mg，每两周一次。迄今为止，受试者接受了27次鞘内HP-β-CD注射。在该受试者中，鞘内HP-β-CD通常安全且耐受性良好。在垂直凝视方面有所改善。受试者发生了亚临床高频听力损失，可能与HP-β-CD相关。血浆24-（S）-羟基胆固醇（中枢神经系统胆固醇再分布的药效学生物标志物）在前5次给药后均显著升高。需要进一步给药以及剂量递增，以更全面地确定鞘内HP-β-CD的安全性和有效性。
Niemann-Pick C, Type 1 (NPC1) is a progressive autosomal recessive neurologic disease caused by defective intracellular cholesterol and lipid trafficking. There are currently no United States Food and Drug Administration approved treatments for NPC1. We undertook a study evaluating the safety, efficacy, and biomarker response of intrathecal 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in a 12-year old subject with mildly symptomatic NPC. The subject received 200mg intrathecal HP-β-CD administered biweekly via lumbar puncture. To date the subject has received 27 intrathecal HP-β-CD injections. Intrathecal HP-β-CD has been generally safe and well tolerated in this subject. There has been improvement in vertical gaze. The subject has developed subclinical hearing loss at high frequency that is likely HP-β-CD related. Plasma 24-(S)-hydroxycholesterol, a pharmacodynamic biomarker for cholesterol redistribution in the central nervous system, was significantly increased in response to each of the first 5 drug administrations. Further dosing as well as dose escalations are needed to more completely ascertain the safety and efficacy of intrathecal HP-β-CD.