Extended Data Fig. 4: PR006 administration leads to transient elevations in plasma progranulin levels of FTD_GRN study participants without pre-existing anti-AAV9 antibodies.
Plasma samples were collected from study participants in the low-dose (2.1 × 1013 vg, n=5) and mid-dose 4.2 × 1013 vg, n=6) cohorts. Progranulin concentrations (ng/mL) in plasma samples were measured by ELISA and plotted against timepoint of collection (baseline, months 1, 2, 3, 6, 9, and 12). At baseline, progranulin concentrations were all below the cut-off value reported by Swift et al.37, denoted in figure by red line). Upon dosing with PR006, at the month 1 timepoint, levels of progranulin concentration increased by 12x to 36x above the respective baseline levels in 8 subjects, which tested negative for anti-AAV9 antibodies at baseline. In the 8 patients the levels generally decreased to baseline within 2–3 months (values not available for 1 subject). Five subjects tested positive for anti-AAV9 antibodies at baseline and showed minimal changes from baseline (0.8x to 1.8x).
