DNL593

DNL593 is an investigational, intravenously administered, brain-penetrant progranulin (PGRN) replacement therapy developed for the treatment of frontotemporal dementia caused by granulin (GRN) gene mutations (FTD-GRN). The drug uses Denali’s Protein Transport Vehicle (PTV) technology to facilitate the delivery of recombinant progranulin across the blood-brain barrier. Mechanistically, DNL593 consists of a progranulin protein fused to an antibody fragment that binds to the transferrin receptor on endothelial cells at the blood-brain barrier, enabling receptor-mediated transcytosis into the central nervous system. By restoring functional PGRN levels in neurons and glia, DNL593 aims to improve lysosomal function and reduce neurodegeneration and microglial dysfunction associated with FTD-GRN. Preclinical studies demonstrated enhanced brain uptake and prevention of neurodegeneration in animal models. As of 2023–2024, DNL593 is being evaluated in a phase 1/2 clinical trial for safety, tolerability, pharmacokinetics, and pharmacodynamics in both healthy volunteers and patients with FTD-GRN[1][2][3][4][5][6][7].

Other names

TAK-594TAK594TAK 594DNL593DNL-593DNL 593PTV:PGRN