Oral Presentation International Congress on Neuronal Ceroid Lipofuscinoses 2025

Initiation of cerliponase alpha at 4-months as pre-symptomatic treatment of CLN2 Batten Disease (127633)

Andrea Miele 1 , Taylor Schwab 2 , Brent O'Neill 3 , Allyson Alexander 1 , Debra Faulk 1 , Leighann Sremba 2 , Stephanie Shea 1 , Stephanie Sims 1 , Jordan Cole 1 , Chelsey Stillman 1 , Jennifer Coffman 2 , Michele Yang 1 , Jennifer Momot 2 , Kourtney Santucci 1 , Scott Demarest 1
  1. University of Colorado SOM/Children's Hospital Colorado, Aurora, Colorado, United States
  2. Children's Hospital Colorado, Aurora, Colorado, United States
  3. PennState Health, Lancaster, Pennsylvania, United States

Background: The enzyme replacement therapy cerliponase alpha is FDA approved to treat individuals with CLN2-related Batten Disease1. However, there is limited guidance for treatment in infancy2.

Methods: Through a neurogenetics outcomes quality improvement project, over three years of clinical care data has been collected prospectively on a patient who began cerliponase alpha treatment at age 4-months for CLN2-related Batten Disease.

Results: The patient was found to have biallelic pathogenic variants in CLN2 via postnatal genetic testing completed due to family history. The decision to treat was made at 3-months old. Following insurance approval for off-label use, the intraventricular reservoir was placed at 3-months 29-days. Cerliponasealpha treatment was initiated at 4-months 4-days old and has continued successfully every 2 weeks. Despite the child’s thinner skull and smaller ventricles, standard placement and use of the codman intraventricular reservoir has been well tolerated without need for replacement. The dosing schedule has been the same as in the clinical trial, which is also the current recommendation on the FDA expanded label, for children under 3-years. From 6 to 12-months of age, the infusion rate was lowered from 2.5ml/hr to 1.66ml/hr, which along with use of a pressure bandage following de-access, successfully reduced post infusion CSF leakage. Anesthesia has varied from inhaled anesthetic to oral midazolam.

Serial 6-month neurological exams have all been normal (CLN2 rating=12, perfect score) with no seizures. Three comprehensive neuropsychological evaluations at ages 18, 25, and 38-months demonstrated age-expected cognitive and motor development, with some variability in language skills. Parent-rated adaptive skills and social emotional development have also been age-appropriate, though with recent slowing in level of independence and some externalizing behaviors.

Conclusions: Cerliponase alpha can be safely administered to children as young as 4-months old but may require minor adjustments. This patient remains asymptomatic, but longer-term follow-up is necessary.

  1. U.S. Food and Drug Administration. FDA approves first treatment for a form of Batten disease. April 27, 2017. Available at https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm555613.htm. Accessed October 2, 2017.
  2. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2024/761052Orig1s014ltr.pdf. Accessed December 3, 2024.