FV 1181. Intracerebroventricular Drug Delivery for CLN2 Disease—5 Years of Experience with ICV Enzyme Replacement Therapy in Hamburg

Background: The intracerebroventricular (ICV) route of administration has been used since 2013 for the delivery of cerliponase α into the central nervous system (CNS) of children with CLN2 disease. However, currently, there is no recommendation how to best perform this 4-hour ICV infusion using this device which was originally designed for children with hydrocephalus or short time treatment of infections or tumors of the CNS. Some long-term data exist from oncological use for chemotherapy, but so far there is no experience regarding infection rates and standard of care when accessing the device for several hours of infusion. At our center, 32 CLN2 patients receive treatment so far.

Aims: To develop a best standard of care practice guideline for ICV infusions at our center, we wanted to collect data on (1) infection risk and (2) device malfunction in our large cohort of 32 patients under regular treatment.

Results: During the course of 2,020 punctures in 4.5 years, we encountered no device malfunctions but 3 infusion-associated device infections which led to exchange of device. Compared with the existing literature (up to 27%), our infection rate (0.14%) is very low. The main bacteria occurring were Cutibacterium acnes (Propionibacterium acnes) and Staphylococcus, which were expected with regard to skin flora. We also investigated typical clinical and laboratory signs for infection with regard to different bacteria and developed a guideline how to best detect infections rapidly but also prevent unnecessary access of the device which again is risk for infection.

Conclusion: ICV infusion drug delivery is an effective and safe way to deliver drugs into the CNS when stringent measures are taken to prevent complications.