Short hairpin RNA treatment improves gait in a mouse model of Charcot‑Marie‑Tooth disease type 1A.

Charcot‑Marie‑Tooth disease (CMT) is the most common inherited neurological disorder of the peripheral nervous system. The major subtype, CMT type 1A (CMT1A), accounts for ~40% of CMT cases and is characterized by distal muscle atrophy and gait disturbances. Short hairpin (sh) RNA sequences are potentially advantageous therapeutic tools for distal muscle atrophy‑induced gait disturbance. Therefore, the current study focused on the effects of an optimal shRNA injection using the myostatin (mstn) gene inhibition system. shLenti‑Mstn A demonstrated significant suppression of endogenous mstn gene expression (>40%) via RT‑qPCR following direct injection into the gastrocnemius and rectus femoris of the hind limb in C22 mice. The results also reported that shLenti‑Mstn A treatment increased muscle mass and size of the hind limbs compared with mock‑treated mice via measurement of the mass of injected muscles and magnetic resonance imaging study. Furthermore, electrophysiological measurement using a Nicolet Viking Quest device revealed significantly improved compound muscle action potential (CMAP) in shLenti‑Mstn A‑treated mice compared with the mock group (P<0.05) whereas nerve conduction velocity (NCV) showed no difference between groups. The shLenti‑Mstn A treatment directly affected increased muscle regeneration, including mass and size, but not regeneration of peripheral nerve. Additionally, shLenti‑Mstn A treatment significantly enhanced mobility, including locomotor coordination (P<0.01) and grip strength of the hindlimbs (P<0.01). Furthermore, MotoRater analysis using real‑time recording with a high‑speed camera revealed that shLenti‑Mstn‑treated mice exhibited an improved walking pattern in terms of step length, base support and duty factor compared with the mock group. It was hypothesized that treatment with shLenti‑Mstn A may provide a novel therapeutic strategy for improving gait in patients with CMT1A.