Oral Presentation International Congress on Neuronal Ceroid Lipofuscinoses 2025

Outcomes of miglustat use in five children with CLN3 disease (127740)

Alexandra M Johnson 1 , Alice E Dutton 2 3 , Ineka T Whiteman 4 5 6 , Michael M Jones 2 7 , Stephanie Crofts 1 , Katie E Geering 8 , Soheil Afshar 9 , John R Grigg 2 3 10
  1. Department of Neurology, Sydney Children’s Hospital, University of New South Wales, Randwick, NSW, Australia
  2. Save Sight Institute, University of Sydney, Sydney, NSW, Australia
  3. Department of Ophthalmology, Sydney Children’s Hospital Network, The Children’s Hospital at Westmead, Westmead, NSW, Australia
  4. BDSRA Australia, Diddillibah, QLD, Australia
  5. BDSRA Foundation, Columbus, OH, USA
  6. Beyond Batten Disease Foundation, Austin, TX, USA
  7. Sydney Children’s Hospital Network, The Children’s Hospital at Westmead, Westmead, NSW, Australia
  8. Department of Orthoptics, The Sydney Children's Hospital Network, Sydney, NSW, Australia
  9. Department of Psychology, Sydney Children's Hospital, Randwick, NSW, Australia
  10. Eye Genetics Research Unit, Children's Medical Research Institute, The University of Sydney and Sydney Eye Hospital, Sydney, NSW, Australia

Objectives: To describe clinical outcomes following oral  miglustat treatment, an approved therapy for related lysosomal diseases, in a small cohort of paediatric patients with CLN3 disease.

Methods: In this retrospective case series, five patients with genetically confirmed classical CLN3 disease were prescribed oral miglustat (weight-based dose to max. 600mg daily), commencing treatment between September 2023 and October 2024. Main outcomes were comprehensive ophthalmological assessment including visual acuity, optical coherence tomography, fundus imaging and fundus autofluorescence. Functional assessments included:, Vineland-3 and Unified Batten Disease Rating Score (UBDRS), as well as observational reports from families, carers and educators

Results: Cohort included five children with classical CLN3 disease, aged between 8 years 10 months and 12 years 10 months (median 9.9 years) at treatment commencement. Vision improvements were reported in several patients with improved visual acuity (logMAR scale) and stabilisation of retinal atrophy. The impact of the therapy was further evidenced by the improved ability to undertake the ophthalmic assessments. Vineland-3 and UBDRS assessments demonstrated stability or improvement for all patients to date. One patient demonstrated improvement in functional/adaptive scoring, though vision has not improved. Some patients have noted a subtle tremor since starting miglustat, which does not appear to impact on function.

Subjective observations from each of the families, carers and educators were grouped by theme with positive reports pertaining to improvements in overall behaviour, decreased aggression and anxiety, improved learning (commensurate with peers for some), increased independence in play and confidence in social interactions. These improvements were often notable as early as the 3 month treatment review).

Conclusions: Miglustat therapy in a cohort of five children with early stage CLN3 disease may have clinically meaningful disease-modifying effects and warrants further prospective studies in paediatric cohorts against known natural history controls, to assess efficacy and long-term treatment outcomes in this population.