This functional benefit obtained thereby by control dogs,although differences did not reach Inhibitors,Modulators,Libraries signifi cance.Neither extension nor flexion force differed sig nificantly between wild type control and NBD treated dogs.Eccentric contraction decrement GRMD dogs,like mdx mice,exhibit a force decrement with eccentric contractions.We Inhibitors,Modulators,Libraries mea sured the degree of ECD of TTJ flexors while a servo motor simultaneously extended the joint.As with our prior study,ECD in GRMD dogs was higher than that of wild type dogs at 6 months.Values in NBD treated dogs after 10 and 30 contractions did not differ from those from the natural history GRMD dogs.Thus,our findings indicate that NBD treatment does not stabilize the muscle cell membrane,in contrast to what would be expected with dystrophin transgenes and sur rogates.

These data Inhibitors,Modulators,Libraries are consistent with our earl ier conclusion in mdx mice that protection of dystrophic muscles through Inhibitors,Modulators,Libraries NFB inhibition does not result from increased membrane stability.The ECD values for control and NBD treated wild type dogs did not differ.Joint angles Joint angles were measured to determine the severity of contractures and overall postural instability.Proximal pelvic limb joint and postural changes in GRMD dogs appear to contribute to their characteristic plantigrade tarsal stance,just as relative sparing of proximal flexor muscles plays a role in distal limb flexor contractures in DMD.Indeed CS muscle circumference cor rected for body weight correlates negatively with TTJ angle in GRMD dogs.This suggests that the hyper trophied CS muscle might play a role analogous to ilioti bial band tightness in DMD.

We measured angles at rest and with maximum flexion and extension at the three pelvic limb joints NBD in GRMD dogs was consistent with that obtained in the mdx murine model of DMD.Interestingly,with both prednisone and NBD treatment,body weight corrected flexion force was reduced in treated versus using a standard technique.Resting Inhibitors,Modulators,Libraries and flexion hip angles were smaller in the NBD treated versus con trol GRMD dogs.To further characterize postural changes typical of GRMD,we measured the pelvic angle formed by the spine and a line drawn between the tuber ischium and the tuber coxae.The pelvic angle values were significantly reduced in NBD treated versus untreated GRMD dogs.Joint angles for control and NBD treated wild type dogs did not differ.

Taken together,joint angle changes in treated GRMD dogs were consistent with less found pronounced postural deformity,which could reflect re duced muscle necrosis inflammation and an associated reduction in flexor muscle hypertrophy.NBD treatment is associated with normalization of MRI features supporting a phenotype of reduced necrosis or inflammation The potential role of MRI as a biomarker in GRMD has been reported in both natural history and preclinical papers.