P.11.16 Three-dimensional gait analysis of Duchenne muscular dystrophy: A trial to evaluate the therapeutic effect of RNA/ENA chimera antisense oligonucleotide that induces dystrophin exon 45 skipping

2013 ◽  
Vol 23 (9-10) ◽  
pp. 803
Author(s):  
Y. Takeshima ◽  
M. Yagi ◽  
T. Lee ◽  
N. Kusunoki ◽  
I. Ojima ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gait Analysis ◽  
Therapeutic Effect ◽  
Antisense Oligonucleotide ◽  
Three Dimensional

scholarly journals The administration of antisense oligonucleotide golodirsen reduces pathological regeneration in patients with Duchenne muscular dystrophy

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Dominic Scaglioni ◽  
Francesco Catapano ◽  
Matthew Ellis ◽  
Silvia Torelli ◽  
Darren Chambers ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Antisense Oligonucleotide ◽  
De Novo ◽  
Exon Skipping ◽  
Significant Negative Correlation ◽  
Entire Cohort ◽  
Associated Proteins ◽  
Analysis Platform ◽  
Dystrophin Protein

AbstractDuring the last decade, multiple clinical trials for Duchenne muscular dystrophy (DMD) have focused on the induction of dystrophin expression using different strategies. Many of these trials have reported a clear increase in dystrophin protein following treatment. However, the low levels of the induced dystrophin protein have raised questions on its functionality. In our present study, using an unbiased, high-throughput digital image analysis platform, we assessed markers of regeneration and levels of dystrophin associated protein via immunofluorescent analysis of whole muscle sections in 25 DMD boys who received 48-weeks treatment with exon 53 skipping morpholino antisense oligonucleotide (PMO) golodirsen. We demonstrate that the de novo dystrophin induced by exon skipping with PMO golodirsen is capable of conferring a histological benefit in treated patients with an increase in dystrophin associated proteins at the dystrophin positive regions of the sarcolemma in post-treatment biopsies. Although 48 weeks treatment with golodirsen did not result in a significant change in the levels of fetal/developmental myosins for the entire cohort, there was a significant negative correlation between the amount of dystrophin and levels of regeneration observed in different biopsy samples. Our results provide, for the first time, evidence of functionality of induced dystrophin following successful therapeutic intervention in the human.

scholarly journals Therapeutic Effect of Camostat Mesilate on Duchenne Muscular Dystrophy in mdx Mice

2003 ◽  
Vol 26 (7) ◽  
pp. 1025-1027 ◽  
Author(s):  
Hitoshi Sawada ◽  
Kazumi Nagahiro ◽  
Yuhsuke Kikukawa ◽  
Susumu Ban ◽  
Reina Kakefuda ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Therapeutic Effect ◽  
Mdx Mice ◽  
Camostat Mesilate

scholarly journals Intravenous Infusion of an Antisense Oligonucleotide Results in Exon Skipping in Muscle Dystrophin mRNA of Duchenne Muscular Dystrophy

2006 ◽  
Vol 59 (5) ◽  
pp. 690-694 ◽  
Author(s):  
Yasuhiro Takeshima ◽  
Mariko Yagi ◽  
Hiroko Wada ◽  
Kazuto Ishibashi ◽  
Atsushi Nishiyama ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Intravenous Infusion ◽  
Antisense Oligonucleotide ◽  
Exon Skipping

scholarly journals A potential therapeutic effect of catalpol in Duchenne muscular dystrophy revealed by binding with TAK1

2020 ◽  
Vol 11 (5) ◽  
pp. 1306-1320 ◽  
Author(s):  
Dengqiu Xu ◽  
Lei Zhao ◽  
Jingwei Jiang ◽  
Sijia Li ◽  
Zeren Sun ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Therapeutic Effect

T.P.1 05 Antisense oligonucleotide design for therapeutic antisense-mediated exon skipping for Duchenne muscular dystrophy

2006 ◽  
Vol 16 (9-10) ◽  
pp. 686
Author(s):  
A. Aartsma-Rus ◽  
C.L. de Winter ◽  
W.E. Kaman ◽  
A.A.M. Janson ◽  
J.C.T. van Deutekom
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Antisense Oligonucleotide ◽  
Exon Skipping

P119: Case study: Can we explain the increased tip-toe gait in a 10-year old boy with Duchenne Muscular Dystrophy by the combination of gait analysis, strength measurements and muscle imaging data?

2017 ◽  
Vol 57 ◽  
pp. 370-371
Author(s):  
Marije Goudriaan ◽  
Catherine Huenaerts ◽  
Nathalie Goemans ◽  
Marleen van den Hauwe ◽  
Simon-Henri Schless ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gait Analysis ◽  
Imaging Data

Gait characteristics in children with Duchenne Muscular Dystrophy during the last 2 years of free ambulation (Preprint)

2021 ◽  
Author(s):  
Juliette Ropars ◽  
Laetitia Houx ◽  
Sylvain Brochard ◽  
François Rousseau ◽  
Carole Vuillerot ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gait Analysis ◽  
Plantar Flexion ◽  
Reaction Force ◽  
Statistical Parametric Mapping ◽  
Initial Contact ◽  
Gait Patterns ◽  
Gait Characteristics ◽  
Abnormal Gait

BACKGROUND Duchenne Muscular Dystrophy (DMD), the most common neuromuscular disease in children, is a severe, progressive disease that affects skeletal muscle. Abnormal gait patterns in children with DMD result from compensatory adaptations of their locomotor system to maintain free ambulation in response to the slow, progressive muscle weakness, contractures and osteoarticular changes caused by the disease. Identification of gait abnormalities can be challenging because current understanding of how gait patterns changes progressively in children with DMD is limited. 3D gait analysis could thus increase understanding about the effects of the disease on gait, guide treatments and help to predict key milestones, such as ambulation loss. This latter event is important because it is an endpoint for clinical trials and studies of DMD disease progression. OBJECTIVE The primary aim of this study was to analyze the gait characteristics of children with Duchenne Muscular Dystrophy (DMD) during their last 2 years of free ambulation. The secondary aim was to explore the capacity of gait variables to predict the time of loss of ambulation. METHODS The gait of eighteen children with DMD and fourteen age-matched control children was recorded using a 3D optoelectronic system. Statistical parametric mapping was used to compare kinematic and kinetic variables between groups. Multivariate regression was used to identify predictors of the time of ambulation loss among spatiotemporal, kinematic and kinetic variables. RESULTS Compared with the controls, anterior pelvic tilt was increased during the whole gait cycle, hip flexion was increased during the second part of stance phase and of the entire swing, knee flexion was increased during swing, dorsiflexion was reduced during stance, and plantar flexion occurred in swing in the DMD group. Maximal ground reaction force, ankle dorsiflexion moment at initial contact, knee power absorption and generation during loading response, and maximal power generation of the hip at the end of stance were all reduced. A combination of gait variables, mostly kinetic, predicted the duration before ambulation loss to be less than three months. CONCLUSIONS The gait of children with DMD who are close to losing ambulation is characterized by specific deviations. The time of ambulation loss was accurately predicted by 3D gait variables, particularly kinetic. Combined with data from the clinical examination, 3D gait analysis provides valuable information to guide physical therapy, including targeted muscle strengthening and stretching, to help patients maintain free ambulation as long as possible.

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