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Source: Neuromuscular Disorders

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Total 1514 results found since Jan 2013.

G.p.43
Myotubular myopathy (XLMTM) is a fatal pediatric disease of skeletal muscle due to mutations in the MTM1 gene. Patients with XLMTM typically present with generalized muscle weakness and respiratory failure. We have previously demonstrated the efficacy of AAV-mediated MTM1 gene therapy in animal models. In order to express MTM1 preferentially in skeletal muscles after systemic gene delivery, we have constructed AAV vectors that contain the Mtm1 cDNA under the potent desmin promoter and a miRNA-208a target sequence for cardiac detargeting.
Source: Neuromuscular Disorders - October 1, 2014 Category: Neurology Authors: , R. Joubert, C. Moal, K. Poulard, S. Martin, A. Vignaud, F. Mavilio, A. Buj-Bello Source Type: research

G.p.42
Among congenital myopathies, X-linked recessive myotubular myopathy is one of the most severe forms. The majority of patients present with severe hypotonia at birth and respiratory insufficiency and most of them die in the first year of life. However, there is phenotypic variability. Here, we report two patients carrying a missense mutation in MTM1 gene and presenting with a mild phenotype. The first boy was born on time with respiratory insufficiency and generalised hypotonia. He required ventilator support for 3weeks, and then he went home without specific care.
Source: Neuromuscular Disorders - October 1, 2014 Category: Neurology Authors: , V. Biancalana, S. Mercier, A. David, G. Fayet, J.M. Mussini, J. Laporte, Y. Pereon Source Type: research

G.p.41
Mutations in the myotubularin gene (MTM1) result in X-linked myotubular myopathy (XLMTM), a fatal pediatric disease of skeletal muscle characterized by small centrally nucleated myofibers containing abnormal mitochondrial accumulations. Patients typically present with severe hypotonia and respiratory failure. Previous local studies in Mtm1-mutant mice demonstrated potential efficacy of gene therapy to treat the disease. We recently reported that administration of adeno-associated virus serotype 8 (AAV8) vector expressing myotubularin under the muscle-specific desmin promoter, delivered systemically in myotubularin deficien...
Source: Neuromuscular Disorders - October 1, 2014 Category: Neurology Authors: D.L. Mack, M. Goddard, J.M. Snyder, J. Doering, M.W. Lawlor, P. Moullier, M. O’Callaghan, A.H. Beggs, F. Mavilio, K. Poulard, V. Latournerie, A. Buj-Bello, Source Type: research

SPEG deficiency is associated with muscle weakness, triad defect, abnormal calcium handling and EC coupling
Centronuclear myopathies (CNM) are a subtype of congenital myopathies (CM) characterized by skeletal muscle weakness and an increase in the number of central myonuclei. We have identified three CNM probands, two with dilated cardiomyopathy, carrying SPEG mutations. SPEG protein localizes to the terminal cisternae of the sarcoplasmic reticulum (SR). We previously described that SPEG interacts with myotubularin, a protein also linked to a type of CNM called myotubular myopathy. Currently, the role of SPEG in muscle function is unclear.
Source: Neuromuscular Disorders - September 10, 2017 Category: Neurology Authors: V. Huntoon, J. Widrick, C. Sanchez, C. Kutchukian, S. Cao, A. Beggs, V. Jacquemond, P. Agrawal Source Type: research

New therapeutic approaches and their readout
Currently there is no cure for muscular dystrophies but recently but promising treatments have emerged, highlighting the need of robust biomarkers. Several biomarkers have been proposed but none of them can monitor drug response longitudinally in a dose-dependent fashion. We recently demonstrated that in an atrophic muscle process, including muscular dystrophies, the myostatin pathway is intrinsically down-regulated to counter balance muscle wasting. This process was reversible in MTM1-deficient myotubular myopathy upon gene transfer leading to reactivation of the myostatin pathway.
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: J. Dumonceaux, V. Mariot, C. Le Guiner, I. Barthelemy, C. Hourd é, M. Montus, S. Blot, T. Voit Source Type: research

Congenital myopathies (cnm)
X-linked myotubular myopathy (XLMTM) is a rare neuromuscular disease with very heterogeneous clinical features varying from mild to severe with a death occurring in the first period of life mostly due to respiratory failure. Long term survivors with severe XLMTM remain often non-ambulant and need ventilation support. Less commonly, patients develop a mild phenotype, sometimes even starting during adulthood. Due to mutations in the  MTM1 gene located on the X-chromosome, the disorder predominantly affects males but female carriers can also develop symptoms.
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: M. Annoussamy, C. Lilien, T. Gidaro, V. Ch ê, U. Schara, A. D'Amico, J. Dowling, B. Darras, A. Daron, M. Mayer, A. Hernandez, C. Vuillerot, S. Fontaine, C. deLattre, R. Bellance, V. Biancalana, A. Buj-Bello, JR. Hogrel, H. Landy, L. Servais, NatHis-MTM Source Type: research

P.105INCEPTUS pre-phase 1, prospective, non-interventional, natural history run-in study to evaluate subjects aged 4 years and younger with X-linked myotubular myopathy (XLMTM)
XLMTM is a rare disease caused by mutations in the MTM1 gene, leading to profound muscle weakness, respiratory failure and early death. INCEPTUS (NCT02704273) is a prospective, non-interventional study in patients (pts) ≤4 years old to characterize the course and natural history of XLMTM using neuromuscular and respiratory assessments and to identify adverse events (AEs). INCEPTUS will generate within-pt control data to support a Phase 1/2 gene therapy clinical trial (ASPIRO). As of 22MAR19, 32 male pts (0.3-4.6 years of age) have been enrolled and assessed every 3 months for up to 24 months.
Source: Neuromuscular Disorders - September 30, 2019 Category: Neurology Authors: L. Servais, P. Shieh, J. Dowling, N. Kuntz, W. M üller-Felber, B. Smith, C. Bönnemann, F. Muntoni, D. Bilder, T. Duong, R. Graham, M. Jain, M. Lawlor, V. MacBean, M. Noursalehi, T. Pitts, G. Rafferty, S. Rico, S. Prasad Source Type: research

Late breaking news e-poster presentation
Skeletal muscle-targeted therapies that increase contractility hold promise for the treatment of neuromuscular diseases. As a compound class, fast skeletal muscle troponin activators (FSTAs) directly increase muscle calcium (Ca ²+) sensitivity and amplify the muscle force response to subtetanic neural stimulation. Disease-modifying therapies like systemic gene transfer have previously been shown to improve muscle function in a canine model of myotubular myopathy. The purpose of the current study was to evaluate the expand ed utility of a canine skeletal muscle model to understand the pharmacokinetic/pharmacodynamic (PK/PD...
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: Dr. Robert W Grange, Dr. Eva R Chin, Dr. Jordan Klaiman, Dr. Darren Hwee, Dr. Bradley Morgan, Dr. Fady Malik, Dr. Martin Childers, Dr. SiWei Luo, Dr. David Mack Source Type: research

Congenital myopathies 2
Myotubular myopathy (MTM) is a devastating childhood muscle disease associated with severe disabilities and early death. Maani et al (2018)., recently identified tamoxifen as a novel therapeutic candidate for MTM that improves muscle structure, strength and prolongs survival in MTM mice through modulation of dynamin-2 (DNM2), a known disease modifier. As clinical trials for tamoxifen in MTM are imminent, there remains a need for a reliable, non-invasive biomarker to reflect disease severity and treatment response, facilitating disease monitoring and testing of novel therapies.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: N. Maani, N. Sabha, D. Gustafson, A. Ramani, J. Fish, M. Alexander, J. Dowling Source Type: research

Congenital myopathies 2
X-linked myotubular myopathy (XLMTM) is a rare congenital neuromuscular disorder affecting boys at a rate of 1 in 50,000 live births. The majority ( ∼80%) of the affected children are born with serious and diffuse skeletal muscle weakness and hypotonia that necessitate immediate and sustained extensive care including tracheostomy and feeding by gastric intubation. Considerable proportions (∼25%) of the cases succumb to death within their fir st year of life and the majority do so later due mainly to respiratory failure.
Source: Neuromuscular Disorders - September 28, 2020 Category: Neurology Authors: M. Ghahramani Seno, J. Volpatti, N. Sabha, C. Alper, E. Sarikaya, J. Dowling Source Type: research

Congenital myopathies – centronuclear myopathies
The mode of inheritance of X-linked myotubular myopathy (XL-MTM) is currently considered recessive and the proportion of manifesting carriers is assumed low. We aimed to characterize the spectrum of clinical signs and symptoms in a cohort of female XL-MTM carriers, including prevalence, genetic features and associated disease burden. We performed a cross-sectional online questionnaire study among XL-MTM carriers, recruiting from patient associations, medical centres and registries in the United Kingdom, Germany and the Netherlands.
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: F. Braun, S. Reumers, J. Spillane, J. Bohm, M. Pennings, M. Schouten, A. van der Kooi, A. Foley, C. B önnemann, E. Kamsteeg, C. Erasmus, U. Schara-Schmidt, H. Jungbluth, N. Voermans Source Type: research

Congenital myopathies – centronuclear myopathies
Breakthrough advances have recently been achieved in therapy development in the neuromuscular disease field, based on promising preclinical data obtained in animal models. Generating reliable preclinical therapeutic data from validated animal models can significantly de-risk drug development by improving trust in the outcome from preclinical studies across study sites. Here we perform statistical analysis and a joint longitudinal-survival modelling of the progressive phenotype observed in Mtm1 −/y knock-out mice, a faithful model for myotubular myopathy, due to myotubularin 1 (MTM1) loss-of-function mutations.
Source: Neuromuscular Disorders - September 19, 2021 Category: Neurology Authors: S. Buono, A. Monseur, A. Menuet, A. Rob é, C. Koch, J. Laporte, L. Thielemans, M. Depla, B. Cowling Source Type: research

X-linked myotubular myopathy
In 1966, Spiro, Shy and Gonatas described the muscle pathology of an adolescent boy with diffuse muscle weakness that included involvement of the facial and extraocular muscles [1]. The appearance of the muscle was reminiscent of fetal myotubes, and the authors termed the condition “myotubular myopathy”. While the precise nature and etiology of the unusual myofibers identified by Spiro remain unclear, the terminology has persisted.
Source: Neuromuscular Disorders - October 1, 2021 Category: Neurology Authors: Michael W. Lawlor, James J. Dowling Tags: Review Source Type: research

P.3.6 Antioxidant capacity is impaired in hyposialylated myotubes of GNE myopathy
GNE myopathy (also known as distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy) is a rare autosomal recessive myopathy characterized by skeletal muscle atrophy and weakness that preferentially involve the distal muscles. The causative GNE gene encodes an essential enzyme in the biosynthesis of sialic acid and hyposialylation is thought to be a key factor in the underlying pathomechanism. We previously found that muscle atrophy appears in the young age of GNE myopathy model mice and is preventable by antioxidant administration, suggesting that oxidative stress would be associated with this primary my...
Source: Neuromuscular Disorders - September 7, 2013 Category: Neurology Authors: A. Cho, M.C. Malicdan, I. Nonaka, Y.K. Hayashi, I. Nishino, S. Noguchi Source Type: research