The devastating paediatric-onset lysosomal storage disorder mucopolysaccharidosis type III syndrome (also known as Sanfilippo syndrome), has been viewed as untreatable. Rapidly progressing neurological impairments lead to death, typically in the second decade of life. In The Lancet Neurology, Marc Tardieu and colleagues1 report the outcomes of a phase 1/2 clinical trial of intracerebral gene therapy with a recombinant adenoassociated viral vector serotype 2/5 encoding human α-N-acetylglucosaminidase (NAGLU) in four young children (age 20–53 months) with mucopolysaccharidosis type IIIB syndrome. This form of the disease results from an inherited NAGLU deficiency. The data are reported for 30 months of follow-up and are important for two reasons. First, this is the longest follow-up period after a therapeutic intervention reported in children with mucopolysaccharidosis type III syndromes, and the data show that the cognitive disease course in this syndrome is modifiable, at least in the short term. Second, the data also highlight a potential therapeutic window of opportunity and suggest that missing this period could lead to suboptimum outcomes. The latter observation is particularly important as it underscores the need for neonatal screening for this (and possibly other) rapidly progressing neurodegenerative disorders.
- gene therapy
- mucopolysaccharidosis type IIIB syndrome
- Sanfilippo syndrome
- lysosomal storage disorder