Short hairpin RNA treatment improves gait in a mouse model of CharcotMarieTooth disease type 1A.
Mol Med Rep
; 22(6): 4947-4955, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-33173958
ABSTRACT
CharcotMarieTooth 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 atrophyinduced gait disturbance. Therefore, the current study focused on the effects of an optimal shRNA injection using the myostatin (mstn) gene inhibition system. shLentiMstn A demonstrated significant suppression of endogenous mstn gene expression (>40%) via RTqPCR following direct injection into the gastrocnemius and rectus femoris of the hind limb in C22 mice. The results also reported that shLentiMstn A treatment increased muscle mass and size of the hind limbs compared with mocktreated 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 shLentiMstn Atreated mice compared with the mock group (P<0.05) whereas nerve conduction velocity (NCV) showed no difference between groups. The shLentiMstn A treatment directly affected increased muscle regeneration, including mass and size, but not regeneration of peripheral nerve. Additionally, shLentiMstn A treatment significantly enhanced mobility, including locomotor coordination (P<0.01) and grip strength of the hindlimbs (P<0.01). Furthermore, MotoRater analysis using realtime recording with a highspeed camera revealed that shLentiMstntreated 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 shLentiMstn A may provide a novel therapeutic strategy for improving gait in patients with CMT1A.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Charcot-Marie-Tooth
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RNA Interferente Pequeno
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Miostatina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2020
Tipo de documento:
Article