Fig 1.
(A) WST1 absorbance as an indicator of cell viability in a tunicamycin challenge assay using fibroblasts derived from G93A-SOD1 mice. (B) WST absorbance indicator a tunicamycin challenge assay using fibroblasts derived from non-transgenic mice. (C) Tunicamycin EC50s as a function of guanabenz concentration in G93A-SOD1 and non-transgenic mouse fibroblasts.
Fig 2.
a) Guanabenz plasma drug levels in G93A-SOD1 mice after i.p. bolus injection of 10 mg/kg guanabenz. b) Relative mRNA expression in spinal cord of mice after continuous subcutaneous infusion of guanabenz at 0.45, 1.5, or 4.5 mg/kg or vehicle control. c) Western blot analysis of Bip, Chop, Bcl2, and Ccnd1 in spinal cord samples from mice treated with 4.5 mg/kg/day guanabenz or vehicle control. d) Relative quantitation of Chop protein determined by western blot in 4.5 mg/kg/day guanabenz treated mice or vehicle treated mice.
Table 1.
Guanabenz Mouse Pharmacokinetics.
Guanabenz plasma pharmacokinetics parameters in G93A-SOD1 mice after i.p. injection of 10 mg/kg guanabenz.
Fig 3.
Average percent mouse body weight change after 28 days.
Fig 4.
Kaplan meier curves of results from efficacy study 4.5 mg/kg/day subcutaneous infusion of guanabenz compared to vehicle control in G93A-SOD1 mice (A) onset of paralysis of male G93A-SOD1 mice, (B) survival of G93A-SOD1 mice, (C) onset of paralysis of female G93A-SOD1 mice, (D) survival of G93A-SOD1 mice, (E) onset of paralysis of all G93A-SOD1 mice, (F) survival of all G93A-SOD1 mice.
Table 2.
Guanabenz Efficacy Study Paralysis Onset Results Summary.
Age at onset of paresis in 4.0 mg/kg qod efficacy study and 4.5 mg/kg/day efficacy study.
Table 3.
Guanabenz Efficacy Study Survival Results Summary.
Age of ALS related death in 4.0 mg/kg qod efficacy study and 4.5 mg/kg/day efficacy study.
Fig 5.
Kaplan meier curves of results from efficacy study 4.0 mg/kg qod intraperitoneal injection of guanabenz compared to vehicle control in G93A-SOD1 mice (A) onset of paralysis of male G93A-SOD1 mice, (B) survival of G93A-SOD1 mice, (C) onset of paralysis of female G93A-SOD1 mice, (D) survival of G93A-SOD1 mice, (E) onset of paralysis of all G93A-SOD1 mice, (F) survival of all G93A-SOD1 mice.