Central nervous system manifestations of mucopolysaccharidosis type I (MPS I) such as cognitive impairment, hydrocephalus, and spinal cord compression are inadequately treated by intravenously-administered enzyme replacement therapy with laronidase (recombinant human alpha-L-iduronidase). While hematopoietic stem cell transplantation treats neurological symptoms, this therapy is not generally offered to attenuated MPS I patients. This study is a randomized, open-label, controlled pilot study of intrathecal laronidase in eight attenuated MPS I patients with cognitive impairment. Subjects ranged between 12 years and 50 years old with a median age of 18 years. All subjects had received intravenous laronidase prior to the study over a range of 4 to 10 years, with a mean of 7.75 years. Weekly intravenous laronidase was continued throughout the duration of the study. The randomization period was one year, during which control subjects attended all study visits and assessments, but did not receive any intrathecal laronidase. After the first year, all eight subjects received treatment for one additional year. There was no significant difference in neuropsychological assessment scores between control or treatment groups, either over the one-year randomized period or at 18 or 24 months. However, there was no significant decline in scores in the control group either. Adverse events included pain (injection site, back, groin), headache, neck spasm, and transient blurry vision. There were seven serious adverse events, one judged as possibly related (headache requiring hospitalization). There was no significant effect of intrathecal laronidase on cognitive impairment in older, attenuated MPS I patients over a two-year treatment period. A five-year open-label extension study is underway.

中文翻译：

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鞘内酶替代治疗I型粘多糖贮积病认知下降的一项随机，开放标签，对照的试验研究。

I型粘多糖贮积病（MPS I）的中枢神经系统表现（如认知障碍，脑积水和脊髓压迫）未通过Laronidase（重组人α-L-艾杜糖醛酸酶）的静脉内酶替代治疗得到充分治疗。虽然造血干细胞移植可治疗神经系统症状，但通常不向减毒的MPS I患者提供此疗法。这项研究是对8例认知功能减退的MPS I减毒患者进行鞘内过氧化氢酶的随机，开放标签，对照先导性研究。受试者年龄在12岁至50岁之间，中位年龄为18岁。在研究之前，所有受试者均在4至10年的时间内接受了静脉内的laronidase酶治疗，平均为7.75年。在整个研究过程中，每周都进行静脉内壬酸酶的继续治疗。随机化期为一年，在此期间，对照受试者参加了所有研究访问和评估，但未接受鞘内过氧化氢酶。第一年之后，所有八名受试者又接受了一年的治疗。对照组或治疗组之间的神经心理学评估评分在一年的随机期间或18或24个月内均无显着差异。但是，对照组的分数也没有显着下降。不良事件包括疼痛（注射部位，背部，腹股沟），头痛，颈部痉挛和短暂的视力模糊。共发生了7例严重不良事件，其中1例可能与疾病有关（头痛需要住院治疗）。在两年的治疗期内，鞘内过氧化物酶对老年减毒的MPS I患者的认知障碍无明显影响。一项为期五年的开放标签扩展研究正在进行中。