Background

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare, autosomal recessive, neurodegenerative lysosomal storage disorder caused by tripeptidyl peptidase 1 (TPP1) deficiency. Cerliponase alfa, a recombinant human TPP1 enzyme, is the first and only approved treatment for CLN2 disease and the first approved enzyme replacement therapy administered via intracerebroventricular (ICV) infusion.

Methods

A meeting of healthcare professionals from US institutions with experience in cerliponase alfa treatment of children with CLN2 disease was held in November 2018. Key common practices were identified, and later refined during the drafting of this manuscript, that facilitate safe chronic administration of cerliponase alfa.

Results

Key practices include developing a multidisciplinary team of clinicians, pharmacists, and coordinators, and institution-specific processes. Infection risk may be reduced through strict aseptic techniques and minimizing connections and disconnections during infusion. The impact of ICV device design on port needle stability during extended ICV infusion is a critical consideration in device selection. Monitoring for central nervous system infection is performed at each patient contact, but with flexibility in the degree of monitoring. Although few institutions had experienced positive cerebrospinal fluid (CSF) test results, the response to a positive CSF culture should be determined on a case-by-case basis, and the ICV device should be removed if CSF infection is confirmed.

Conclusions

The key common practices and flexible practices used by institutions with cerliponase alfa experience may assist other institutions in process development. Continued sharing of experiences will be essential for developing standards and patient care guidelines.

中文翻译：

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脑室内神经脂蛋白阿尔法治疗神经元性2类脂褐素沉着病2型疾病：来自美国临床的临床实践考虑。

背景

神经元2类脂褐质病（CLN2）是一种罕见的常染色体隐性，神经退行性溶酶体贮积病，由三肽基肽酶1（TPP1）缺乏引起。重组人TPP1酶Cerliponase alfa是CLN2疾病的第一个也是唯一获得批准的治疗方法，并且是通过脑室内（ICV）输注进行的第一个获得批准的酶替代疗法。

方法

2018年11月，举行了一次来自美国机构的针对CLN2病患儿童进行神经脂酶酶治疗的经验的美国医疗保健专家会议。确定了关键的常规做法，并在本手稿起草时进行了完善，以利于安全地长期施用神经脂酶酶。

结果

关键实践包括建立临床医生，药剂师和协调员的多学科团队，以及针对特定机构的流程。通过严格的无菌技术和减少输液过程中的连接和断开，可以降低感染风险。在延长ICV输注期间，ICV设备设计对端口针头稳定性的影响是设备选择中的关键考虑因素。每次患者接触时都进行中枢神经系统感染的监测，但监测程度具有灵活性。尽管很少有机构对脑脊液（CSF）的检测结果呈阳性，但应根据具体情况确定对CSF阳性培养的反应，如果确诊为CSF感染，则应移除ICV装置。

结论

具有cerliponase alfa经验的机构所使用的关键通用实践和灵活实践可能会帮助其他机构进行过程开发。不断分享经验对于制定标准和患者护理指南至关重要。