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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: Aggregate-selective antibody attenuates seeded aggregation but not spontaneously evolving disease in SOD1 ALS model mice

Fig. 3

αSOD1143–153 prolongs survival of hSOD1 seed inoculated hSOD1G85R Tg mice. a Overview of experimental protocol in the hSOD1-inoculation mouse model. Aggregate seeds prepared from terminal stage hSOD1G85R Tg spinal cords were incubated with mAb αSOD1143–153 or vehicle control prior to seed inoculation into the lumbar spinal cord (L2–L3 level) of pre-symptomatic Tg hSOD1G85R mice. b Kaplan–Meier plot show post-inoculation survival of hSOD1G85R mice. Seeds and mAbs were incubated at equal molar ratio (1 ng seeds + 1× αSOD1143–153) (dark red line; n = 6) or 10-times the molar ratio of mAb (1 ng seeds + 10× αSOD1143–153) (light red; n = 6). Analyzed as one group, mice inoculated with seeds mixed with αSOD1143–153 (n = 6 + 6) had a significantly longer post-inoculation survival time compared to mice inoculated with seeds mixed with PBS vehicle, (1 ng seeds + vehicle) (black line; n = 6; p < 0.05). For dilution effect comparison, another group of mice were inoculated with diluted seeds (0.33 ng seeds + vehicle) (dashed black line; n = 6). The total injection volume in each mouse was 1 μL of the respective preparation. Survival time of non-inoculated control hSOD1G85R Tg mice from the same colony is included for comparison (dotted black line; n = 44). Non-inoculated control values are presented as age of sacrifice minus mean inoculation age (107 days) for the treated groups. c Scheme for mAb injection in the hSOD1G85R seed inoculation mouse model: Once weekly systemic administration of mAbs via i.p injection (day 0), was initiated 3 weeks before hSOD1G85R aggregate seeds were inoculated into the lumbar spinal cord (day 28, one day after the 4th mAb injection). Antibodies were injected i.p. once per week until the mouse reached terminal disease stage. d Kaplan–Meier plot showing survival in days post hSOD1G85R aggregate seed inoculation. Treatments using 10 mg/kg αSOD165–72 (light green; n = 5), 10 mg/kg αSOD1143–153 (light red; n = 5) or 50 mg/kg control IgG (grey; n = 9) had no significant effect on survival compared to no mAb control treatment (black; n = 9). Treatment with 50 mg/kg αSOD165–72 (green; n = 5) significantly decreased survival (see Table 1). Treatment with 50 mg/kg αSOD1143–153 (red; n = 9) significantly extended survival. For comparison, survival of non-inoculated control hSOD1G85R transgenic mice is shown as black dotted line (n = 44) and represents age at end-stage disease minus 100-days, the mean age at seed inoculation

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