Oral Presentation International Congress on Neuronal Ceroid Lipofuscinoses 2025

Intravitreal Enzyme Replacement Therapy to Prevent Retinal Disease Progression in Children with Neuronal Ceroid Lipofuscinosis Type 2 (CLN2):  Interim 3-Year Safety and Efficacy Outcomes (123244)

Catherine O. Jordan 1 , Emily De Los Reyes 1 , Thomas A. Mendel 2 , Brian Caprul 1 , Sarah Podlasiak 1 , David L. Rogers 1
  1. Nationwide Children's Hospital, Columbus, OHIO, United States
  2. Ophthalmology, The Ohio State University , Columbus, Ohio, United States

Introduction:  Classic late infantile neuronal ceroid lipofuscinosis (CLN2) is caused by a biallelic mutation of the TPP1 gene. Vision loss begins around age four, resulting in blindness by age 7-10.  Cerliponase alfa (Brineura, BioMarin) is indicated to slow the loss of ambulation in pediatric patients with CLN2. However, treated children continue to experience visual loss. Intravitreal cerliponase alfa allows the enzyme to target tissues in the eye, offering a potential treatment. 

Methods: We designed a Phase I/II randomized, masked, clinical trial to determine the safety and efficacy of intravitreal cerliponase alfa in preventing retinal disease progression in children with CLN2 currently receiving intraventricular cerliponase alfa. One eye was randomly assigned to monthly treatment for 12-months, bilateral treatment followed for an additional 12-months. Patients that developed disease progression based on Weill Cornell Ophthalmic Severity scores (WCOSS) began bilateral treatment early.

Results:  Five patients were enrolled, 3 males and 2 females with an average age of 5.17 yrs.  Over three years, 168 intravitreal injections of cerliponase alfa were performed. There were no serious safety events. Three patients had non-study eye disease progression and began bilateral injections prior to 12-months.  Using a linear mixed model, the predicted value of treatment effect on average central retinal thickness was 8.48 microns.  Subset analysis of the two patients with WCOSS of 1 at baseline showed a 50% decrease in the rate of retinal thining compared to natural history and stabilization of outer retinal architecture based on OCT imaging.

Conclusion/Relevance:  Our study found intravitreal cerliponase alfa was safe.  Treated eyes showed a slower rate of disease progression relative to controls.  Eyes with early disease at baseline demonstrated the largest treatment effect, while those with late-stage disease at presentation showed minimal improvement. Our study provides support for intravitreal treatment with cerliponase alfa in children with CLN2.

  1. Dulz S. et al. Ongoing retinal degeneration despite intraventricular enzyme replacement therapy with cerliponase alfa in late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2 disease). Br J Ophthalmol. 2023 Oct;107(10):1478-1483
  2. Orlin A et al. Spectrum of ocular manifestations in CLN2-associated batten (Jansky-Bielschowsky) disease correlate with advancing age and deteriorating neurological function. PLoS One 2013 Aug 28;8(8):e73128.