Table 2 Summary of PGRN therapeutics and their mechanisms of action

DNL593

Direct replacement with brain-penetrant progranulin construct

PR006

Recombinant Adeno-associated virus (rAAV)-mediated gene therapy to increase progranulin expression in the CNS

PBFT02

Recombinant Adeno-associated virus (rAAV)-mediated gene therapy to increase progranulin expression in the CNS

ARKD-104

Small molecule “progranulin enhancer”; full mechanism not described

AL001 (Latozinemab)

Blocks sortilin-mediated trafficking of progranulin. Increases extracellular progranulin without compromising intracellular levels