Figure 2.

Behavioral Analysis of PMD Mice after Lonaprisan Therapy

(A) Lonaprisan long-term treatment downregulated Plp1 mRNA overexpression.

(B) Regular grid test analyses counting the number of slips were performed at the beginning at 3 weeks of age, at 7 and 10 weeks, and finally at the end at 13 weeks of age.

(C and D) Differences between Lonaprisan-treated PMD mice (n = 11) (filled squares) and placebo-treated control mice (n = 12) (circles) increased with age and became significant at 13 weeks of age at study end (C), which is illustrated in higher magnification of the final time point. Wild-type values (n = 30) are depicted for comparison (open bar) (D).

(E) Plp1 mRNA expression correlated with the grid test analysis, strongly suggesting a direct effect of Plp1 expression on the motor phenotype.

(F) By applying a clinical score in a descriptive analysis, PMD mice showed a pathologic phenotype and Lonaprisan increased the percentage of mice showing solely ataxic gait or even healthy condition.

(G and H) A significant body weight loss was already present in 3-week-old PMD mice (n = 12) compared to the wild-type situation (n = 30). This difference remained present throughout the study. In contrast, PMD placebo controls and Lonaprisan-treated PMD mice (n = 11) did not show any body weight differences at study start and Lonaprisan therapy did not alter the body weight by study end.

ns indicates not significant, ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, shown mean ± SEM.