Development of the “Hamburg Best Practice Guidelines for ICV−Enzyme Replacement Therapy (ERT) in CLN2 Disease” Based on 6 Years of Treatment Experience in 48 Patients

Background: Intracerebroventricular enzyme replacement therapy (ICV-ERT) for CLN2 disease represents the first approved treatment for NCL diseases. It is the first treatment where a recombinant lysosomal enzyme, cerliponase alfa, is administered into the lateral cerebral ventricles to reach the central nervous system, the organ affected in CLN2 disease. If untreated, CLN2 children show first symptoms such as epilepsy and language developmental delay at 2 to 4 years followed by rapid loss of motor and language function, vision loss and early death. Treatment with cerliponase alfa has shown to slow down the rapid neurologic decline. However, the mode of administration by 4-hour-long ICV infusions every 14 days represents a potentially greater risk of infection compared to intravenous ERTs. The Hamburg NCL Specialty Clinic was the first site worldwide to perform ICV-ERT in children with CLN2 disease.

Methods: In order to ensure maximum patient safety, we analyzed data from our center from more than 3,000 ICV-ERT in 48 patients over 6 years regarding the occurrence of device-related adverse events and device infections. Since starting ICV-ERTs, we have also developed and continuously improved the “Hamburg Best Practice Guidelines for ICV–Enzyme Replacement Therapy (ERT) in CLN2 Disease.”

Results: The results of this study showed that the incidence of both malfunction and infection of the Rickham reservoirs was very low at 0.27 and 0.33%, respectively, compared to values in other studies in the literature.

Conclusion: By following our internal procedural guidelines, standardization and patient safety of ICV-ERT for CLN2 disease can be improved.

Publication History

Article published online:
28 October 2021