2B7 Fabs extend life-span and improve motor neuron performance and phenotype in a mouse model of ALS.
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In transgenic SOD1 G93A mutant mice, non-binding control Ig or 2B7 Fabs were injected intraperitoneally 3x/week at 0.5 mg/kg (~10 μg per dose). Treatments were initiated at day ~100 and continued until day ~168. Experiments were done double-blinded, and 2B7 FAb was coded TX1. n = 12 mice per group. The p values in survival and Rotarod Kaplan-Meier plots are derived from log-rank tests.(A) 2B7 Fab treatment significantly extended life-span, p<0.037 versus control. The time at which therapy ended is indicated by red arrows. (B) 2B7 Fab treatment significantly improved Rotarod performance. Shown are 1x per week measurements starting at post-natal day ~100, p<0.01 versus control. The time-course of drug-treatment is indicated by the red line. (C) 2B7 Fab treatment improved or maintained body weight. Shown are 1x per week measurements starting at post-natal day ~100. The time-course of drug-treatment is indicated by the red line. (D) The spinal cords of wild type control, and 2B7-treated or Ig-treated ALS mice were dissected at day 160 (n = 2 per group). Cryosections were studied using fluorescent microscopy after immunostaining with anti-ChAT antibodies (a marker of motor neuron cell body) or anti-VAchT antibodies (a marker of motor neuron cell body and fibers). The ChAT and VAchT phenotype appears to be improved in 2B7-treated G93A ALS mice.