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Total 11221 results found since Jan 2013.
Peliosis hepatis in a child with myotubular myopathy: Successful treatment using hepatic artery embolization
Abstract: Peliosis hepatis (PH) is a rare condition characterized by multiple blood-filled spaces within the hepatic parenchyma that can lead to fatal hemorrhage. There is no consensus on the best treatment algorithm for PH, and therapy is directed at removing the potential causative agent with operative intervention when necessary. Here we present the first known case of PH in a child with myotubular myopathy who was successfully treated with angiography and hepatic artery embolization as a first line therapy, without the need for operative intervention. Awareness of this condition and the available treatment modalities m...
Source: Journal of Pediatric Surgery - August 1, 2013 Category: Surgery Authors: Joseph P. Terlizzi, Robert Azizi, Monica D. Chow, Sharon Underberg-Davis, John L. Nosher, Perry W. Stafford, Joelle Pierre Tags: Journal of Pediatric Surgery Electronic Pages (Available only online at www.jpedsurg.org) Source Type: research
Ultrasound assessment of the diaphragm: Preliminary study of a canine model of x‐linked myotubular myopathy
Discussion: This pilot demonstrates the feasibility of using ultrasound for quantitative assessment of the diaphragm in a canine model. Ultrasonography may potentially replace invasive measures of diaphragm function in canine models and in humans in the future, for non‐invasive respiratory monitoring and evaluation of neuromuscular disease. © 2014 Wiley Periodicals, Inc.
Source: Muscle and Nerve - May 23, 2014 Category: Internal Medicine Authors: Aarti Sarwal, Michael S. Cartwright, Francis O. Walker, Erin Mitchell, Anna Buj‐Bello, Alan H. Beggs, Martin K. Childers Tags: Short Report Source Type: research
G.P.41: Canine X-linked myotubular myopathy: A dose-finding study of systemic AAV8-MTM1 effects on muscle strength, gait, respiration, neuromuscular function and survival
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 - September 4, 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, M. Childers Source Type: research
G.P.43: Gene replacement therapy of myotubular myopathy: Restricting expression of MTM1 in skeletal muscle
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. We show that intravenous delivery of this vector leads to myotubularin expression in s...
Source: Neuromuscular Disorders - September 4, 2014 Category: Neurology Authors: L. Buscara, R. Joubert, C. Moal, K. Poulard, S. Martin, A. Vignaud, F. Mavilio, A. Buj-Bello Source Type: research
Gait characteristics in a canine model of X-linked myotubular myopathy
X-linked myotubular myopathy (XLMTM) is a fatal pediatric disease where affected boys display profound weakness of the skeletal muscles. Possible therapies are under development but robust outcome measures in animal models are required for effective translation to human patients. We established a naturally-occurring canine model, where XLMTM dogs display clinical symptoms similar to those observed in humans. The aim of this study was to determine potential endpoints for the assessment of future treatments in this model.
Source: Journal of the Neurological Sciences - August 29, 2014 Category: Neurology Authors: Melissa A. Goddard, Emily Burlingame, Alan H. Beggs, Anna Buj-Bello, Martin K. Childers, Anthony P. Marsh, Valerie E. Kelly Source Type: research
X-linked myotubular myopathy in females
X-linked myotubular myopathy (XLMTM) is a rare congenital muscle disorder due to mutation in MTM1, encoding myotubularin, a key protein of muscle cell differentiation and intracellular organelle dynamics. Affected males present at birth with severe generalized hypotonia, feeding difficulties and respiratory insufficiency. Most of them die in infancy. Female carriers are usually asymptomatic but seldom show muscle weakness possibly due to skewed X-inactivation. A characteristic morphological alteration named “necklace fibers” has been reported as the histological marker of manifesting MTM1 carriers.
Source: Neuromuscular Disorders - September 11, 2015 Category: Neurology Authors: C. Fiorillo, F. Fattori, G. Astrea, M. Pedemonte, A. Rubegni, F. Trucco, A. Tessa, M. Savarese, J. Baldacci, P. Broda, E. Bertini, C. Minetti, V. Nigro, C. Bruno, F. Santorelli Source Type: research
Peripheral vein injection of AAV8-MTM1 leads to long-term survival and correction of severe muscle pathology in a canine model of X-linked myotubular myopathy: Results from a dose escalation study
Mutations in the myotubularin gene (MTM1) result in X-linked myotubular myopathy (XLMTM), a fatal pediatric disease of the skeletal muscle characterized by small centrally nucleated myofibers containing abnormal mitochondrial accumulations. Patients typically present with severe hypotonia and respiratory failure. Previous studies in Mtm1 mutant mice demonstrated efficacy of gene therapy to treat the disease. We also previously reported that administration of an adeno-associated virus serotype 8 (AAV8) vector expressing myotubularin under the muscle-specific desmin promoter via high pressure regional hind limb perfusion pro...
Source: Neuromuscular Disorders - September 11, 2015 Category: Neurology Authors: D. Mack, K. Poulard, M. Goddard, J. Snyder, R. Grange, J. Doering, J. Strande, V. Latournerie, P. Veron, L. Yang, L. Buscara, C. Le Bec, S. Martin, M. O'Callaghan, F. Mingozzi, A. Beggs, M. Lawlor, F. Mavilio, M. Childers, A. Buj-Bello Source Type: research
Audentes enrols first patient in INCEPTUS study for X-Linked Myotubular Myopathy
Audentes Therapeutics has reported that the first patient has been enrolled in INCEPTUS, a study to characterise the disease presentation in children suffering with X-Linked Myotubular Myopathy (XLMTM).
Source: Drug Development Technology - August 18, 2016 Category: Pharmaceuticals Source Type: news
PIK3C2B inhibition improves function and prolongs survival in myotubular myopathy animal models
Myotubular myopathy (MTM) is a devastating pediatric neuromuscular disorder of phosphoinositide (PIP) metabolism resulting from mutations of the PIP phosphatase MTM1 for which there are no treatments. We have previously shown phosphatidylinositol-3-phosphate (PI3P) accumulation in animal models of MTM. Here, we tested the hypothesis that lowering PI3P levels may prevent or reverse the MTM disease process. To test this, we targeted class II and III PI3 kinases (PI3Ks) in an MTM1-deficient mouse model. Muscle-specific ablation of Pik3c2b, but not Pik3c3, resulted in complete prevention of the MTM phenotype, and postsymptomat...
Source: Journal of Clinical Investigation - August 22, 2016 Category: Biomedical Science Authors: Nesrin Sabha, Jonathan R. Volpatti, Hernan Gonorazky, Aaron Reifler, Ann E. Davidson, Xingli Li, Nadine M. Eltayeb, Claudia Dall’Armi, Gilbert Di Paolo, Susan V. Brooks, Ana Buj-Bello, Eva L. Feldman, James J. Dowling Source Type: research
ASO-mediated Dnm2 knockdown prevents and reverts myotubular myopathy in mice
Centronuclear myopathies (CNM) are severe muscle diseases characterized by muscle weakness and hypotrophic fibers with centralized nuclei. The most severe and neonatal X-linked form is known as myotubular myopathy and caused by loss-of-function mutations in myotubularin (MTM1), while the main autosomal-dominant form is due to mutations in Dynamin2 (DNM2). However, no specific therapy is available for patients. Therefore, there is an urgent need to validate therapeutic approaches for such devastating diseases.
Source: Neuromuscular Disorders - September 10, 2016 Category: Neurology Authors: H. Tasfaout, S. Buono, S. Guo, C. Kretz, B. Monia, B. Cowling, J. Laporte Source Type: research
Prolonged benefit from systemic rAAV8 in a canine model of myotubular myopathy
Mutations in MTM1 result in X-linked myotubular myopathy (XLMTM), a rare neuromuscular disease that causes devastating muscular weakness in affected children, often fatal in the first years of life. We previously demonstrated the therapeutic efficacy of intravenous delivery of recombinant adeno-associated viral vectors (rAAV) expressing myotubularin in murine and canine animal models of the disease. Here, we report clinical and physiological outcomes more than 3 years after a single intravenous infusion of AAV8-MTM1 in two dogs.
Source: Neuromuscular Disorders - September 10, 2016 Category: Neurology Authors: M. Elverman, D. Mack, K. Poulard, M. Goddard, J. Snyder, R. Grange, V. Latournerie, P. Veron, H. Meng, F. Mingozzi, M. Lawlor, A. Beggs, M. Childers, A. Buj-Bello Source Type: research
AAV-mediated MTMR2 delivery prolongs survival and rescues the pathology in a mouse model of myotubular myopathy
X-linked myotubular myopathy (XLMTM) is a severe congenital disorder leading to generalized skeletal muscle weakness in male infants, frequently associated with fatal respiratory failure. The disease is caused by loss-of-function mutations in the MTM1 gene, which encodes myotubularin, the founder member of a family of 15 homologous proteins in mammals (including MTMR1 to 14). We recently demonstrated the therapeutic efficacy of intravenous delivery of recombinant adeno-associated viral vectors (rAAV) expressing myotubularin in murine and canine animal models of the disease.
Source: Neuromuscular Disorders - September 10, 2016 Category: Neurology Authors: N. Dani èle, C. Moal, L. Julien, T. Jamet, R. Joubert, S. Martin, A. Vignaud, M. Lawlor, A. Buj-Bello Source Type: research
X-linked myotubular myopathy in ambulant patients
X-linked myotubular myopathy (XLMTM) is a rare disease of skeletal muscle due to mutations in the MTM1 gene. Most patients have the severe generalized form and develop serious life-threatening complications at or shortly after birth. Long term survivors with severe XLMTM remain often non-ambulant and need ventilation support and assistance for normal daily activities. Less commonly patients develop a mild phenotype, sometimes even starting during adulthood. The disorder predominantly affects males but female carriers can also develop symptoms.
Source: Neuromuscular Disorders - September 10, 2016 Category: Neurology Authors: M. Annoussamy, V. Ch ë, C. Lilien, T. Gidaro, A. Daron, M. Mayer, J. Arnal, C. Wallgren-Pettersson, V. Biancalana, J. Laporte, J. Hogrel, D. Ramsdell, H. Landy, A. Buj-Bello, L. Servais Source Type: research
Long ‐term effects of systemic gene therapy in a canine model of myotubular myopathy
This article is protected by copyright. All rights reserved.
Source: Muscle and Nerve - March 29, 2017 Category: Internal Medicine Authors: Matthew Elverman, Melissa A Goddard, David Mack, Jessica M Snyder, Michael W Lawlor, Hui Meng, Alan H Beggs, Ana Buj ‐Bello, Karine Poulard, Anthony P Marsh, Robert W Grange, Valerie E. Kelly, Martin K Childers Tags: Research Article Source Type: research
Grand paternal inheritance of X-linked myotubular myopathy due to mosaicism, and identification of necklace fibers in an asymptomatic male
• An unusual family with grand paternal transmission of X-linked myotubular myopathy.• Genetic analysis identified a novel mutation in myotubularin (MTM1).• Muscle pathology demonstrated necklace fibers in the asymptomatic grandfather.• The results indicate postzygotic mosaicism in the grand father.
Source: Neuromuscular Disorders - May 9, 2017 Category: Neurology Authors: Carola Hedberg-Oldfors, Kittichate Visuttijai, Alexandra Topa, Mar Tulinius, Anders Oldfors Tags: Case report Source Type: research
