mRNA as a Novel Treatment Strategy for Hereditary Spastic Paraplegia Type 5.

Hereditary spastic paraplegia type 5 is a neurodegenerative disease caused by loss-of-function mutations in the gene encoding the oxysterol 7-α-hydroxylase involved in bile acid synthesis in the liver. Lack of CYP7B1 leads to an accumulation of its oxysterol substrates, in particular 25-hydroxycholesterol and 27-hydroxycholesterol that are able to cross the blood-brain barrier and have neurotoxic properties. A potential therapeutic strategy for SPG5 is the replacement of CYP7B1 by administration of mRNA.