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Electrophysiologic biomarkers for assessing disease progression and the effect of riluzole in SOD1 G93A ALS mice.

Li J, Sung M, Rutkove SB - PLoS ONE (2013)

Bottom Line: No difference in clinical disease onset or survival was found between treated and untreated groups.In addition, all methods failed to identify any beneficial effect of riluzole.However, EIM phase shows early linear declines, supporting its potential as a useful new biomarker for preclinical drug testing.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.

ABSTRACT

Objective: To compare electrical impedance myography (EIM) 50 kHz phase to weight, motor score, paw grip endurance (PGE), CMAP amplitude, and MUNE for the identification of disease progression and the effect of riluzole in the SOD1 G93A mouse.

Methods: Twenty-three animals received 8 mg/kg/day riluzole in the drinking water starting at 6 weeks of age; 22 animals served as controls. Weight, motor score, PGE, CMAP, MUNE, and EIM were performed weekly to evaluate disease progression.

Results: No difference in clinical disease onset or survival was found between treated and untreated groups. In addition, all methods failed to identify any beneficial effect of riluzole. Thus, data from all animals were combined for additional analyses. Of the 4 parameters, EIM phase showed the earliest change from baseline and the most linear decline throughout the entire measurement period. In addition, EIM phase correlated with PGE, CMAP amplitude, and MUNE (Spearman r = 0.92, 0.90, and 0.72, respectively, p<0.01 for all). The rate of EIM phase decline also correlated with individual animal survival (Spearman r = -0.31, p<0.05).

Conclusions: At this dose, riluzole is ineffective in slowing progression of ALS. However, EIM phase shows early linear declines, supporting its potential as a useful new biomarker for preclinical drug testing.

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Related in: MedlinePlus

Kaplan-Meier Curves showing survival and disease onset based on standard clinical measures.a. Disease onset, b. Survival.
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pone-0065976-g001: Kaplan-Meier Curves showing survival and disease onset based on standard clinical measures.a. Disease onset, b. Survival.

Mentions: Figure 1 shows Kaplan-Meier curves for both the untreated and treated animals. The mean clinical disease onset for untreated animals was no different from the treated animals (120.1±1.3 days versus 118.3±1.4, respectively, p = 0.35, Figure 1a). The mean survival for the untreated group was not different from that of the treated group (136.1±1.6 days versus 132.4±1.8 days, respectively, p = 0.13, Figure 1b). Based on the standard deviations of the group survival values and the number of animals in each group, there had been approximately an 86% power to detect a 7.5 day prolongation in survival (p<0.05, one-tailed).


Electrophysiologic biomarkers for assessing disease progression and the effect of riluzole in SOD1 G93A ALS mice.

Li J, Sung M, Rutkove SB - PLoS ONE (2013)

Kaplan-Meier Curves showing survival and disease onset based on standard clinical measures.a. Disease onset, b. Survival.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675066&req=5

pone-0065976-g001: Kaplan-Meier Curves showing survival and disease onset based on standard clinical measures.a. Disease onset, b. Survival.
Mentions: Figure 1 shows Kaplan-Meier curves for both the untreated and treated animals. The mean clinical disease onset for untreated animals was no different from the treated animals (120.1±1.3 days versus 118.3±1.4, respectively, p = 0.35, Figure 1a). The mean survival for the untreated group was not different from that of the treated group (136.1±1.6 days versus 132.4±1.8 days, respectively, p = 0.13, Figure 1b). Based on the standard deviations of the group survival values and the number of animals in each group, there had been approximately an 86% power to detect a 7.5 day prolongation in survival (p<0.05, one-tailed).

Bottom Line: No difference in clinical disease onset or survival was found between treated and untreated groups.In addition, all methods failed to identify any beneficial effect of riluzole.However, EIM phase shows early linear declines, supporting its potential as a useful new biomarker for preclinical drug testing.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.

ABSTRACT

Objective: To compare electrical impedance myography (EIM) 50 kHz phase to weight, motor score, paw grip endurance (PGE), CMAP amplitude, and MUNE for the identification of disease progression and the effect of riluzole in the SOD1 G93A mouse.

Methods: Twenty-three animals received 8 mg/kg/day riluzole in the drinking water starting at 6 weeks of age; 22 animals served as controls. Weight, motor score, PGE, CMAP, MUNE, and EIM were performed weekly to evaluate disease progression.

Results: No difference in clinical disease onset or survival was found between treated and untreated groups. In addition, all methods failed to identify any beneficial effect of riluzole. Thus, data from all animals were combined for additional analyses. Of the 4 parameters, EIM phase showed the earliest change from baseline and the most linear decline throughout the entire measurement period. In addition, EIM phase correlated with PGE, CMAP amplitude, and MUNE (Spearman r = 0.92, 0.90, and 0.72, respectively, p<0.01 for all). The rate of EIM phase decline also correlated with individual animal survival (Spearman r = -0.31, p<0.05).

Conclusions: At this dose, riluzole is ineffective in slowing progression of ALS. However, EIM phase shows early linear declines, supporting its potential as a useful new biomarker for preclinical drug testing.

Show MeSH
Related in: MedlinePlus