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Tirasemtiv amplifies skeletal muscle response to nerve activation in humans.

Hansen R, Saikali KG, Chou W, Russell AJ, Chen MM, Vijayakumar V, Stoltz RR, Baudry S, Enoka RM, Morgans DJ, Wolff AA, Malik FI - Muscle Nerve (2014)

Bottom Line: The deep fibular nerve was stimulated transcutaneously to activate the tibialis anterior muscle and produce dorsiflexion of the foot.The data confirm that tirasemtiv amplifies the response of skeletal muscle to nerve input in humans.This outcome provides support for further studies of tirasemtiv as a potential therapy in conditions marked by diminished neuromuscular input.

View Article: PubMed Central - PubMed

Affiliation: Research and Early Development, Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California, 94080-4808, USA.

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Related in: MedlinePlus

Tirasemtiv increases the response of muscle to neuromuscular activation in a dose- and concentration-related manner. (A) The placebo-subtracted summed mean percent change from baseline of peak force (%ΣF) is plotted in (A) (± SEM) from each assessment time-point for 250-, 500-, and 1000-mg doses. Asterisks denote statistical significance (P < 0.05) compared with placebo. The lines with circles, squares, and triangles are the average plasma concentrations for each population for the 250-, 500-, and 1000-mg doses, respectively. (B) The placebo-subtracted percent change in peak force (%F) is plotted. Mean ± SEM data for each tirasemtiv plasma level concentration bin are plotted for each stimulus frequency. Asterisks denote statistical significance (P < 0.05).
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fig02: Tirasemtiv increases the response of muscle to neuromuscular activation in a dose- and concentration-related manner. (A) The placebo-subtracted summed mean percent change from baseline of peak force (%ΣF) is plotted in (A) (± SEM) from each assessment time-point for 250-, 500-, and 1000-mg doses. Asterisks denote statistical significance (P < 0.05) compared with placebo. The lines with circles, squares, and triangles are the average plasma concentrations for each population for the 250-, 500-, and 1000-mg doses, respectively. (B) The placebo-subtracted percent change in peak force (%F) is plotted. Mean ± SEM data for each tirasemtiv plasma level concentration bin are plotted for each stimulus frequency. Asterisks denote statistical significance (P < 0.05).

Mentions: Tirasemtiv increased the placebo-corrected summed percent change from baseline of peak force (ΣF) in a dose-dependent manner (Fig. 2A). Statistically significant increases in force relative to pre-dose baseline values when compared with placebo occurred at doses of 500 and 1000 mg at all time-points and for all comparisons between 250 and 1000 mg (P < 0.05). Although comparisons of intermediate dose steps (i.e., 250–500 or 500–1000 mg) did not generally reach statistical significance, the overall dose dependence was strongly significant statistically at all time-points (P < 0.002). Forces increased between the 1- and 3-hour time-points commensurate with the rise in tirasemtiv plasma concentrations; the increases in force were maintained out to the last time-point measured at 7 hours, as were tirasemtiv plasma concentrations.


Tirasemtiv amplifies skeletal muscle response to nerve activation in humans.

Hansen R, Saikali KG, Chou W, Russell AJ, Chen MM, Vijayakumar V, Stoltz RR, Baudry S, Enoka RM, Morgans DJ, Wolff AA, Malik FI - Muscle Nerve (2014)

Tirasemtiv increases the response of muscle to neuromuscular activation in a dose- and concentration-related manner. (A) The placebo-subtracted summed mean percent change from baseline of peak force (%ΣF) is plotted in (A) (± SEM) from each assessment time-point for 250-, 500-, and 1000-mg doses. Asterisks denote statistical significance (P < 0.05) compared with placebo. The lines with circles, squares, and triangles are the average plasma concentrations for each population for the 250-, 500-, and 1000-mg doses, respectively. (B) The placebo-subtracted percent change in peak force (%F) is plotted. Mean ± SEM data for each tirasemtiv plasma level concentration bin are plotted for each stimulus frequency. Asterisks denote statistical significance (P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260123&req=5

fig02: Tirasemtiv increases the response of muscle to neuromuscular activation in a dose- and concentration-related manner. (A) The placebo-subtracted summed mean percent change from baseline of peak force (%ΣF) is plotted in (A) (± SEM) from each assessment time-point for 250-, 500-, and 1000-mg doses. Asterisks denote statistical significance (P < 0.05) compared with placebo. The lines with circles, squares, and triangles are the average plasma concentrations for each population for the 250-, 500-, and 1000-mg doses, respectively. (B) The placebo-subtracted percent change in peak force (%F) is plotted. Mean ± SEM data for each tirasemtiv plasma level concentration bin are plotted for each stimulus frequency. Asterisks denote statistical significance (P < 0.05).
Mentions: Tirasemtiv increased the placebo-corrected summed percent change from baseline of peak force (ΣF) in a dose-dependent manner (Fig. 2A). Statistically significant increases in force relative to pre-dose baseline values when compared with placebo occurred at doses of 500 and 1000 mg at all time-points and for all comparisons between 250 and 1000 mg (P < 0.05). Although comparisons of intermediate dose steps (i.e., 250–500 or 500–1000 mg) did not generally reach statistical significance, the overall dose dependence was strongly significant statistically at all time-points (P < 0.002). Forces increased between the 1- and 3-hour time-points commensurate with the rise in tirasemtiv plasma concentrations; the increases in force were maintained out to the last time-point measured at 7 hours, as were tirasemtiv plasma concentrations.

Bottom Line: The deep fibular nerve was stimulated transcutaneously to activate the tibialis anterior muscle and produce dorsiflexion of the foot.The data confirm that tirasemtiv amplifies the response of skeletal muscle to nerve input in humans.This outcome provides support for further studies of tirasemtiv as a potential therapy in conditions marked by diminished neuromuscular input.

View Article: PubMed Central - PubMed

Affiliation: Research and Early Development, Cytokinetics, Inc., 280 East Grand Avenue, South San Francisco, California, 94080-4808, USA.

Show MeSH
Related in: MedlinePlus