Delivering the message: mRNA replacement reaches the liver in Niemann-Pick type C1 disease

Niemann-Pick type C1 (NPC1) disease is an autosomal recessive lysosomal storage disorder affecting both neuronal and peripheral tissues. Several NPC1 mutations impair cholesterol export from late endosomes and lysosomes, leading to lipid accumulation, impaired autophagy, mitochondrial stress, inflammation, and progressive injury in the liver and central nervous system. Although the conditions can be severe, available therapeutic options remain limited. In this issue of Molecular Therapy Nucleic Acids, Koufer and colleagues reported results from an in vivo evaluation of an mRNA-based NPC1 replacement therapy.