J. Eidahl, M. Hoover, O. Branson, M. Freitas, S. Harper

J. Eidahl, M. Hoover, O. Branson, M. Freitas, S. Harper September 11, 2017

The DUX4 gene associated with Facioscapulohumeral muscular dystrophy (FSHD) encodes a transcription factor protein that is toxic when expressed in numerous organisms. We hypothesized that one avenue for developing an FSHD treatment could involve inhibiting DUX4 protein activity. However, little is known about the mechanisms that may confer toxic properties to the DUX4 protein.… Read More...

M. Miyakawa, T. Yonekawa, M. Malicdan, E. Lach-Trifilieff, I. Nonaka, I. Nishino, S. Noguchi September 11, 2017

GNE myopathy is a debilitating autosomal recessive myopathy due to mutations in the GNE gene, UDP-N-acetylglucosamine-2-epimerase/ N-Acetylmannosamine kinase, which encodes critical enzymes for sialic acid biosynthesis. Clinically, it is characterized by atrophy and weakness in distal skeletal muscle. We have established that a key factor in the mechanism of disease is sialic acid deficiency, a target for recent and ongoing clinical trials.… Read More...

V. Mariot, R. Joubert, C. Hourdé, L. Féasson, M. Hanna, F. Muntoni, T. Maisonobe, L. Servais, R. Le Panse, O. Benveniste, T. Stojkovic, P. Machado, T. Voit, A. Buj-Bello, J. Dumonceaux September 11, 2017

Myostatin being a negative regulator of muscle mass, its down-regulation has been seen as a promising tool to counterbalance the muscle wasting observed in neuromuscular patients. However, so far, the clinical trials have been very disappointing and clinical endpoints have been barely reached.… Read More...

A. Puma, M. Garibaldi, E. Teveroni, G. Deidda, F. Moretti, S. Sacconi September 11, 2017

Facioscapulohumeral muscular dystrophy is characterized by genetic/epigenetic heterogeneity and intrafamilial and interfamilial clinical variability. Part of this variability is related to genetic/epigenetic factors such as the residual number of D4Z4 repeats on permissive chromosome(s) 4, the presence of mutation in chromatin modifiers genes.… Read More...

Y. Maeda, Y. Yonemochi, Y. Nakajyo, H. Hidaka, T. Ikeda, Y. Ando September 11, 2017

Muscle satellite cells are essential for muscle regeneration. However, efficient regeneration does not occur without muscle-resident mesenchymal progenitor cells. We show first that bone marrow-derived mesenchymal stromal cells (Bm-MSCs) also facilitate muscle regeneration in Duchenne muscular dystrophy (DMD) model mice. Bm-MSCs transplanted into peritoneal cavities of DMD model mice with severe muscle degeneration strongly suppressed dystrophic pathology and improved death-related symptoms, which resulted in dramatic lifespan extension.… Read More...

E. Mercuri, N. Goemans, F. Muntoni, A. Manzur, B. Wong, J. Signorovitch, S. Ward September 11, 2017

Although the Duchenne community has collected a wealth of natural history data, translating those data in clinical trial design has proven challenging. Clinical trials have suffered from higher than anticipated variance, masking potential drug effects. The predominant driver of this variance is phenotypic heterogeneity in disease progression.… Read More...

J. de Greef, Y. Krom, B. den Hamer, L. Snider, Y. Hiramuki, R. van den Akker, D. Salvatori, R. Tawil, M. Blewitt, S. Tapscott, S. van der Maarel September 11, 2017

A copy of the DUX4 retrogene is located in each repeat unit of the D4Z4 macrosatellite repeat that typically consists of 8–100 units. DUX4 is a double homeobox transcription factor that is expressed in the luminal cells of the testis but not in somatic cells due to repeat-mediated epigenetic repression.… Read More...

E. Mercuri, N. Goemans, G. Sajeev, Z. Yao, E. McDonnell, S. Ward, J. Signorovitch September 11, 2017

Natural history (NH) controls can be attractive in rare diseases such as DMD because they enable smaller drug trials with faster enrollment. Well-known challenges include potential bias due to differences in outcome assessment, and concern that ‘better’ outcomes in clinical trials could arise from more regular follow-up and greater hope for improvement than in NH, especially for effort-based outcomes like 6MWD.… Read More...

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