Oral Presentation International Congress on Neuronal Ceroid Lipofuscinoses 2025

Real-world pre-symptomatic treatment in CLN2 disease: Learnings from families with multiple affected children (126745)

Lena Marie Westermann 1 , Lara Yasmin Ruhberg 2 , Luca Hagenah 2 , Christoph Schwering 2 , Miriam Nickel 2 , Angela Schulz 2 3
  1. University Children´s Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland
  2. University Children´s Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, HAMBURG, Germany
  3. German Center for Child and Adolescent Health (DZKJ), partner site Hamburg, Hamburg, Germany

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a neurodegenerative lysosomal storage disorder. Without treatment, symptoms begin between 1.5 and 4 years of age, followed by rapid functional decline. Intracerebroventricular enzyme replacement therapy with Cerliponase alfa is the only approved therapy. Data from clinical trials show significant increase of therapy efficacy in patients with treatment start < 2 years.

We studied 14 families with at least two siblings affected by CLN2. In all cases, diagnosis of the older sibling enabled earlier diagnosis and treatment of younger ones. Treatment efficacy was assessed using longitudinal Hamburg motor-language (ML) scores and developmental performance in gross motor, fine motor, language, and personal-social domains using the Denver II Scale. All data were normalized to the family-specific mean age of symptom onset, and patients were grouped by disease stage at treatment start: pre-symptomatic (PreTx), early-symptomatic (EarlyTx), moderate-symptomatic (ModTx), and untreated (NoTx).

PreTx patients showed the longest preservation of ML function. None in this group reached an ML score of 0 (complete function loss) during the observation period of max. 9.25 years of age, and the time to first ML score of 3 (marked function loss) was significantly delayed compared to all other groups. EarlyTx patients also showed delayed progression to ML scores of 3 and 0 compared to NoTx individuals. ModTx patients showed no improvement in time to ML score of 3 but a slower decline to ML score of 0. In terms of early development, PreTx patients outperformed all other groups across Denver II subdomains and frequently acquired new skills.

These findings underscore the benefit of pre-symptomatic treatment in CLN2 disease reflected by longer preservation of motor and language function and improved early childhood development. Therefore, early diagnosis is critical and newborn screening pilot studies need to be brought more into the focus of NCL research.