Antisense oligonucleotide-based therapeutic strategy for progranulin-deficient frontotemporal dementia

摘要: Loss-of-function GRN mutations result in progranulin haploinsufficiency and are a common cause of frontotemporal dementia (FTD). 1, 2 Antisense oligonucleotides (ASOs) are emerging as a promising therapeutic modality for neurological diseases, 3, 4 but ASO-based strategies for increasing target protein levels are still relatively limited. Here, we report the use of ASOs to increase progranulin protein levels by targeting the miR-29b binding site in the 3’UTR of the GRN mRNA, resulting in increased translation.