A Novel In Vivo‐Active Small Molecule Inducer of Progranulin for the Treatment of Frontotemporal Dementia

Heterozygous mutations in GRN that lead to haploinsufficiency of the progranulin (PGRN) protein cause the fatal neurodegenerative disease frontotemporal dementia (FTD‐GRN). Complete loss of PGRN, on the other hand, leads to an early onset lysosomal storage disorder, indicating a critical role for PGRN in the lysosome. Although its exact function is unknown, PGRN is both secreted and trafficked to the lysosome where it is processed into granulins. Lysosomal granulins are reported to modulate the activity of lysosomal enzymes. Currently there are no treatments for FTD‐GRN but restoring PGRN to normal levels is a promising therapeutic strategy.