Mouse Anti Human Dystrophin Hybridoma [NBOEZT213(8E3)]

Background: Duchenne muscular dystrophy is an X-linked muscle disease caused by dystrophin absence. Muscle weakness is a major determinant of the gait impairments in patients with Duchenne muscular dystrophy and it affects lower limbs more often than upper limbs. Monitoring progression of motor symptoms is key to plan treatments for prolonging ambulation. Methods: The progression of gait impairment in a group of ten patients with Duchenne muscular dystrophy was observed longitudinally three times over a period of 2 years by computerized gait analysis system. Spatio-temporal parameters of gait, and variability indicators were extracted from kinematics, while lower limb muscles coactivation were measured at the baseline and at each follow-up evaluation. The 6-min walk test was used to evaluate functional capacity at each time session. Findings: We found a significant increase in stride width and in both stride width and stride length variability at the 1-and 2-year follow-up evaluations. Furthermore, significant higher values in proximal muscle coactivation and significant lower values in both distal muscle coactivation and functional capacity were found at the 2-year follow-up evaluation. Significant negative correlations between muscle coactivation at proximal level and functional capacity and between muscle coactivation at distal level and gait variability were observed. Interpretation: Our findings suggest that patients with Duchenne muscular dystrophy exhibit decline in functional capacity after 2 years from the baseline. Moreover, to cope with disease progression, patients try to maintain an effective gait by changing the balance dynamic strategies (i.e. increase in proximal muscle coactivation) during the course of disease.

Extracellular matrix (ECM) components play an important role in maintaining skeletal muscle function, but excessive accumulation of ECM components interferes with skeletal muscle regeneration after injury, eventually inducing fibrosis. Increased oxidative stress level caused by dystrophin deficiency is a key factor in fibrosis in Duchenne muscular dystrophy (DMD) patients. Mesenchymal stem cells (MSCs) are considered a promising therapeutic agent for various diseases involving fibrosis. In particular, the paracrine factors secreted by MSCs play an important role in the therapeutic effects of MSCs. In this study, we investigated the effects of MSCs on skeletal muscle fibrosis. In 2-5-month-old mdx mice intravenously injected with 1 x 10(5)Wharton's jelly (WJ)-derived MSCs (WJ-MSCs), fibrosis intensity and accumulation of calcium/necrotic fibers were significantly decreased. To elucidate the mechanism of this effect, we verified the effect of WJ-MSCs in a hydrogen peroxide-induced fibrosis myotubes model. In addition, we demonstrated that matrix metalloproteinase-1 (MMP-1), a paracrine factor, is critical for this anti-fibrotic effect of WJ-MSCs. These findings demonstrate that WJ-MSCs exert anti-fibrotic effects against skeletal muscle fibrosis, primarily via MMP-1, indicating a novel target for the treatment of muscle diseases, such as DMD.