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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

Weekly measures for riluzole and non-riluzole treated animals.a. 50 kHz phase, b. Paw grip endurance, c. CMAP amplitude, d. MUNE, e. weight, f. motor score. Open circles, untreated; closed circles, treated.
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pone-0065976-g002: Weekly measures for riluzole and non-riluzole treated animals.a. 50 kHz phase, b. Paw grip endurance, c. CMAP amplitude, d. MUNE, e. weight, f. motor score. Open circles, untreated; closed circles, treated.

Mentions: As shown is Figure 2a–f, none of the rates of decline for EIM, PGE, CMAP amplitude, MUNE, weight or motor score showed significant difference between untreated and treated animals, from 6 weeks of age until death, although there was a non-significant difference in weight (Figure 2e). This data is also summarized in Table 1, which shows the individual slopes of decline over time for each parameter (including EIM resistance and reactance) for riluzole-treated and untreated animals.


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)

Weekly measures for riluzole and non-riluzole treated animals.a. 50 kHz phase, b. Paw grip endurance, c. CMAP amplitude, d. MUNE, e. weight, f. motor score. Open circles, untreated; closed circles, treated.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065976-g002: Weekly measures for riluzole and non-riluzole treated animals.a. 50 kHz phase, b. Paw grip endurance, c. CMAP amplitude, d. MUNE, e. weight, f. motor score. Open circles, untreated; closed circles, treated.
Mentions: As shown is Figure 2a–f, none of the rates of decline for EIM, PGE, CMAP amplitude, MUNE, weight or motor score showed significant difference between untreated and treated animals, from 6 weeks of age until death, although there was a non-significant difference in weight (Figure 2e). This data is also summarized in Table 1, which shows the individual slopes of decline over time for each parameter (including EIM resistance and reactance) for riluzole-treated and untreated animals.

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