FIG. 1.
Pharmacological effects of DFP in a murine model of ALS. Data are mean ± SEM in all experiments and doses, n = 10 per group for each sex and each dose. For the females, the best dose was 50 mg/kg/day, the dose of 100 mg/kg/day was less effective, and the dose of 200 mg/kg/day was not inefficient. For the males, the only efficient dose was 200 mg/kg/day. All the figures are presented with the dose of 50 mg/kg/day for the females and 200 mg/kg/day for the males. (A) The survival rates were significantly improved for female (in red) and male (in black) SOD1G86R mice (from disease and treatment onset onward) in the DFP group (solid line) and the vehicle group (Veh, dotted line) (log-rank test; females: p = 0.011; males: p = 0.03). (B) Change in body weight in female and male SOD1G86R mice from disease and treatment onset until death, in four groups: WT-Veh (black triangles with a dotted line), WT-DFP (red triangles with a solid line), SOD1G86R-Veh (black circles with a dotted line), and SOD1G86R-DFP (red circles with a solid line) (ANCOVA adjusted on baseline, *p < 0.05 vs. untreated SOD1G86R mice). (C) The peak NeuroScore (a quick phenotypic neurological scoring system for evaluating disease progression in the mouse model of ALS: 0: no impairment; 6: greatest possible impairment) in the SOD1G86R-Veh group (black bar) and the SOD1G86R-DFP group (red bar) (Mann–Whitney test, *p < 0.05 vs. untreated SOD1G86R mice). (D) As measured by qRT-PCR, acetylcholine receptor subunit γ receptor RNA expression as a percentage (%) of the control value in the left gastrocnemius muscle in SOD1G86R female mice treated with 50 mg/kg/day DFP (Mann–Whitney test, *p < 0.05 vs. untreated SOD1G86R mice). (E) Magnetic resonance imaging of the cervical spinal cord at day 70 (i.e., just before the appearance of symptoms and treatment onset) and at day 100 (i.e., with marked motor impairments before death) in untreated female SOD1G86R mice (triangles with a black solid line), WT female mice (squares with a dotted line), and SOD1G86R female mice treated with 50 mg/kg/day DFP (red line). R2* ( = 1/T2*) was obtained in a manually drawn region of interest using a monoexponential fitting of the signal decay with the echo time (Kruskal–Wallis test *p < 0.05 vs. untreated SOD1G86R mice, #p < 0.05 vs. WT untreated mice). (F) Serum ferritin levels (ng/mL) from serum obtained at end of treatment: not significantly reduced after 50 mg/kg/day and 100 mg/kg/day (data not shown), but significantly reduced after 200 mg/kg/day (Kruskal–Wallis test *p < 0.05 vs. untreated SOD1G86R mice). ALS, amyotrophic lateral sclerosis; DFP, deferiprone; SOD, superoxide dismutase; WT, wild type. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars