Figure 3: NMR imaging and spectroscopy analyses of muscles of GRMD dogs injected with rAAV2/8-Spc5.12-cMD1 by the LR route.

(a) Representative example of transverse fat-saturated T2-weighted NMR image of the two forelimbs obtained in dog LR2. At 3 months after injection, signal muscle intensities were decreased and more homogeneous in the injected forelimb (**) compared with the noninjected one. (b) Representative example of ³¹P-NMR spectra of the injected (blue curve) and noninjected forelimb (red curve) of the same dog (LR2). Phosphocreatine (PCr) was increased and inorganic phosphates (Pi) and phosphodiesters (PDE) were decreased relative to ATP in the injected forelimb compared with the noninjected forelimb. (c) NMR imaging fat-saturated (FS) T2w/T1w muscle signal ratio obtained from three different muscles (ECR (extensor carpi radialis brevis), ECRl (extensor carpi radialis longus) and FCU (flexor carpi ulnaris)). The values of this index in the injected forelimb (red closed symbols) were decreased compared with the values obtained in the noninjected forelimb (open red symbols) or in untreated GRMD dogs (yellow symbols), and they were closer to the healthy dog (WT) indices (black symbols). (d) NMR spectroscopy Pi/γATP muscle signal ratios of the injected (red closed symbols) and noninjected forelimbs (open red symbols) as compared with untreated GRMD (yellow symbols) and healthy (WT) controls (black symbols).