Fig. 5.

Latozinemab decreases sortilin in WBCs and increases PGRN levels in the plasma and CSF of HVs and aFTD-GRN participants. A–B Median percentage change from baseline in sortilin in WBCs from HVs who were administered a SAD of latozinemab A and from aFTD-GRN participants who received a single injection of 60-mg/kg latozinemab B. For the HV SAD groups A, n = 4–13 participants/group/timepoint and for the aFTD-GRN group B, n = 3–5 participants/timepont. C–D Median percentage change from baseline in PGRN levels in plasma from HVs C and from the aFTD-GRN group D. For the HV SAD groups C, n = 4–13 participants/group/timepoint and for the aFTD-GRN group D, n = 5 at all timepoints, except on days 2 (30 h post dose), 57, 85, and 113 (n = 3) E–F Median percent change from baseline in PGRN levels in CSF from HVs E and from the aFTD-GRN group F; note that CSF samples were not collected for HVs in the 2-mg/kg and 6-mg/kg dose groups. For the HV SAD groups E, n = 2–13 participants/group/timepoint and for the aFTD-GRN group F, n = 5 at baseline and day 13 and n = 1 at day 25. Nominal timepoints are relative to the end of infusion. The percent change from baseline was calculated for each individual based on their own predose value. Dashed lines indicate baseline. aFTD-GRN, asymptomatic carriers of GRN mutations causative of frontotemporal dementia; HV, healthy volunteer; PGRN, progranulin