Figure 1.

A single dose of neuron-binding human antibody improves NAA concentrations in the brainstem. (A) A representative 300 MHz, ¹H spectra collected at the mouse brainstem. N-acetyl-aspartate (NAA) marked to the right is the dominant peak. (B) Groups of 9 to 13 SJL/J mice at 90 days post-TMEV infection, the time when NAA levels begin to fall and large-axon loss is detectable, were given a single 100 μg dose of HIgM12, isotype IgM control, or PBS i.p. MRS at the brainstem was collected before and at 5 and 10 weeks following the treatment. NAA concentrations were calculated from the spectra. Compared to pre-treatment, NAA increased in the HIgM12-treated group after 10 weeks (P < 0.001). NAA in the control IgM-treated group did not change (P = 0.188); in the PBS-treated group, it decreased after 10 weeks (P = 0.027). (C) After the last MRS measurements, mice were sacrificed, brains removed and processed for pathology analysis. Brainstem pathological scores (means ± SEM) were similar across treatment groups (P = 0.51). (D) Brainstem NAA concentrations plotted against the brainstem pathological score showed no correlation (P = 0.59). (E) Changes in the individual NAA concentrations were calculated at the final time point versus before treatment. NAA levels were considered improved if the difference (NAA^10wk − NAA^before) was higher than or equal to 2 × baseline SEM. Fischer’s exact test was performed, and the control IgM-treated group did not differ from PBS-treated group (P = 0.388). The HIgM12-treated group differed from both control groups (vs control IgM, P = 0.0001 and vs PBS, P = 0.001).