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

Loss-of-function GRN mutations result in progranulin haploinsufficiency and are a common cause of frontotemporal dementia (FTD). Antisense oligonucleotides (ASOs) are emerging as a promising therapeutic modality for neurological diseases, 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. ### Competing Interest Statement K.L., P.J.-N., and F.R. are paid employees of Ionis Pharmaceuticals. Saint Louis University has filed for a patent based on using GRN ASOs to treat frontotemporal dementia. The authors declare no other competing financial interests.