Uk Experience of Managing Metachromatic Leukodystrophy In The Advent of Stem Cell Gene Therapy

Objectives: Metachromatic leukodystrophy (MLD) is a devastating neurodegenerative disorder, and patients with the late infantile (LI) form typically do not survive beyond the first decade. Atidarsagene autotemcel, a haematopoietic stem cell-based gene therapy, is now licensed in the UK for use in pre-symptomatic LI and pre and early symptomatic early juvenile (EJ) MLD. We present early data on children referred to the service since its launch. Methods: We reviewed case notes of all patients referred to the sole referral unit in the UK between February 2022 and August 2023. Results: 24 children were referred; 22 from within the UK. 5/24 were eligible and treated within 12 weeks. 3/5 were pre-symptomatic LI-MLD; 2 with older affected siblings and 1 diagnosed on research newborn screening. All 3 remained asymptomatic to date (current ages: 2 years, 15 months and 15 months). 2/5 were early symptomatic EJ and were 6 years at diagnosis. One became less ambulant around the time of treatment alongside cognitive deterioration, which then stabilised 3 months later. The other remains independently ambulant with ataxia with stable cognitive abilities. 19/24 were ineligible for treatment (17/19 symptomatic LI-MLD; 2/19 late symptomatic EJ). Conclusions: Although we have successfully treated 5/24 children with gene therapy, majority of referrals were ineligible. Our data highlights the importance of research work in newborn screening to aid early diagnosis and therapy in these patients.