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Second-generation compound for the modulation of utrophin in the therapy of DMD.

Guiraud S, Squire SE, Edwards B, Chen H, Burns DT, Shah N, Babbs A, Davies SG, Wynne GM, Russell AJ, Elsey D, Wilson FX, Tinsley JM, Davies KE - Hum. Mol. Genet. (2015)

Bottom Line: This results in improved sarcolemmal stability and prevents dystrophic pathology through a significant reduction of regeneration, necrosis and fibrosis.All these improvements combine to protect the mdx muscle from contraction induced damage and enhance physiological function.This detailed evaluation of the SMT C1100 drug series strongly endorses the therapeutic potential of utrophin modulation as a disease modifying therapeutic strategy for all DMD patients irrespective of their dystrophin mutation.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK, simon.guiraud@dpag.ox.ac.uk kay.davies@dpag.ox.ac.uk.

No MeSH data available.


Related in: MedlinePlus

SMT022357 protects the muscle against damage and improves the muscle function. The difference in force produced between the first and fifth stretch is represented as a sensitive indicator of the resistance of the muscle to stretch-induced damage. EDL muscles were stretched at 15% of their fibre length whilst contracting tetanically. Values are mean ± SEM of n = 10 per group; **P < 0.01, ***P < 0.001.
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DDV154F6: SMT022357 protects the muscle against damage and improves the muscle function. The difference in force produced between the first and fifth stretch is represented as a sensitive indicator of the resistance of the muscle to stretch-induced damage. EDL muscles were stretched at 15% of their fibre length whilst contracting tetanically. Values are mean ± SEM of n = 10 per group; **P < 0.01, ***P < 0.001.

Mentions: Furthermore, we investigated if the increased membrane stability and reduction in pathology achieved by SMT022357 treatment translated into functional improvements in muscle. Ex vivo analysis of EDL muscles after 5 weeks of daily SMT022357 treatment demonstrated that after five eccentric contractions, SMT022357 results in a 50% (P = 0.004) decrease in force drop compared with vehicle-treated mdx mice (Fig. 6). No changes were observed in muscle mass, absolute or specific force when treated with SMT022357 in comparison to the vehicle (data not shown).Figure 6.


Second-generation compound for the modulation of utrophin in the therapy of DMD.

Guiraud S, Squire SE, Edwards B, Chen H, Burns DT, Shah N, Babbs A, Davies SG, Wynne GM, Russell AJ, Elsey D, Wilson FX, Tinsley JM, Davies KE - Hum. Mol. Genet. (2015)

SMT022357 protects the muscle against damage and improves the muscle function. The difference in force produced between the first and fifth stretch is represented as a sensitive indicator of the resistance of the muscle to stretch-induced damage. EDL muscles were stretched at 15% of their fibre length whilst contracting tetanically. Values are mean ± SEM of n = 10 per group; **P < 0.01, ***P < 0.001.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492389&req=5

DDV154F6: SMT022357 protects the muscle against damage and improves the muscle function. The difference in force produced between the first and fifth stretch is represented as a sensitive indicator of the resistance of the muscle to stretch-induced damage. EDL muscles were stretched at 15% of their fibre length whilst contracting tetanically. Values are mean ± SEM of n = 10 per group; **P < 0.01, ***P < 0.001.
Mentions: Furthermore, we investigated if the increased membrane stability and reduction in pathology achieved by SMT022357 treatment translated into functional improvements in muscle. Ex vivo analysis of EDL muscles after 5 weeks of daily SMT022357 treatment demonstrated that after five eccentric contractions, SMT022357 results in a 50% (P = 0.004) decrease in force drop compared with vehicle-treated mdx mice (Fig. 6). No changes were observed in muscle mass, absolute or specific force when treated with SMT022357 in comparison to the vehicle (data not shown).Figure 6.

Bottom Line: This results in improved sarcolemmal stability and prevents dystrophic pathology through a significant reduction of regeneration, necrosis and fibrosis.All these improvements combine to protect the mdx muscle from contraction induced damage and enhance physiological function.This detailed evaluation of the SMT C1100 drug series strongly endorses the therapeutic potential of utrophin modulation as a disease modifying therapeutic strategy for all DMD patients irrespective of their dystrophin mutation.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK, simon.guiraud@dpag.ox.ac.uk kay.davies@dpag.ox.ac.uk.

No MeSH data available.


Related in: MedlinePlus