Skip to main content
. Author manuscript; available in PMC: 2018 Sep 5.
Published in final edited form as: Nat Med. 2018 Mar 5;24(4):427–437. doi: 10.1038/nm.4500

Figure 3. MEPB improves phenotypic outcomes and pathologic degeneration in a pilot preclinical trial in SBMA mice.

Figure 3

(a) Mean body weight of AR121Q mice from 4 weeks until 8 weeks of age. (b) Mean rotarod performance of AR121Q mice from 5 weeks until 7 weeks of age. (c) Mean grip strength (measured as grams force) of all four paws of AR121Q mice. Data shown in a-c were evaluated by one-way ANOVA with repeated measures followed by Sidak’s posthoc analysis for all pairwise comparisons. **P = 0.007 (a), *P = 0.043 and 0.044 for TA and MEPB at 5 weeks, **P = 0.01 at 7 weeks vs vehicle treated (b), *P = 0.032 at 6 weeks, *P = 0.012, **P = 0.001 at 7 weeks vs 5 weeks (c). (d) Kaplan-Meier survival estimation of AR121Q mice (log-rank test). (e) Quantification of footprint/gait analysis of AR121Q mice. Average stride length and forepaw and hindpaw overlap are depicted. n = 2, 1, and 3 mice for vehicle, TA, and MEPB treated NTG group, n = 4, 5, and 3 mice for vehicle, TA, and MEPB treated AR121Q group. All graphs represent mean ± s.e.m. (f) Video stills of clasping behavior in representative NTG and AR121Q mice from three independent experiments. (g) Representative spinal cord sections from AR121Q mice treated with vehicle, TA, or MEPB from one independent experiment. Sections were stained with AR (N20), ubiquitin, or polyQ (5TF1-1C2) antibodies. Arrowheads indicate the presence of ubiquitin-positive nuclear inclusions. (h) Representative skeletal muscle sections (gastrocnemius/soleus) from AR121Q mice treated with vehicle, TA, or MEPB from one independent experiment. Sections were stained with H&E or Gomori trichrome stain for muscle morphology, in addition to ubiquitin antibody. Dotted lines trace around representative myofibers, demonstrating differences in myofiber size. Arrows indicate atrophied myofibers. Arrowheads indicate myofibers containing centralized nuclei. Vehicle is 1% DMSO in corn oil administered three times per week; TA is 50 mg/kg administered three times per week; and MEPB is 50 mg/kg administered three times per week. Scale bars represent 50 μm.