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Total 11221 results found since Jan 2013.
Expression of the neuropathy-associated MTMR2 gene rescues MTM1-associated myopathy
Myotubularins are active or dead phosphoinositides phosphatases defining a large protein family conserved through evolution and implicated in different neuromuscular diseases. Loss-of-function mutations in myotubularin (MTM1) cause the severe congenital myopathy called myotubular myopathy (or X-linked centronuclear myopathy) while mutations in the myotubularin-related protein MTMR2 cause Charcot-Marie-Tooth peripheral neuropathy (CMT4B1). Here we aimed to determine the functional specificity and redundancy of MTM1 and MTMR2, and to assess their abilities to compensate for a potential therapeutic strategy.
Source: Neuromuscular Disorders - September 10, 2017 Category: Neurology Authors: M. Raess, B. Cowling, D. Bertazzi, C. Kretz, B. Rinaldi, P. Kessler, S. Friant, J. Laporte Source Type: research
X-linked myotubular myopathy: Living longer and awaiting treatment
The congenital myopathies (CMs) are a cluster of genetic disorders affecting myofiber structure and function. The salient clinical features are hypotonia, weakness, and motor impairment. The presentation varies from the most severe impairment in the newborn to a range of phenotypes in infancy ("floppy baby"), childhood, or occasionally adulthood. The prevalence of CMs is 1:26,000 children (birth to 17 years).1 The CMs were named on the basis of distinctive morphologic abnormalities seen on muscle biopsy: nemaline myopathy, with rods due to protein accumulation; core myopathy, with cores or multiminicores devoid of oxidativ...
Source: Neurology - September 25, 2017 Category: Neurology Authors: Finkel, R. S., Darras, B. T. Tags: EDITORIALS Source Type: research
Tamoxifen increases survival, improves motor function and reduces levels of BIN1 and DNM2 in a mouse model of X-linked centronuclear (myotubular) myopathy
X-Linked centronuclear myopathy (XLCNM) is a rare and severe congenital myopathy characterised by generalised muscle weakness and abnormal nuclei positioning. Most affected boys die in their first year of life and survivors fail to achieve independent ambulation. It is caused by mutations in the Mtm1 gene encoding myotubularin, a ubiquitously expressed phosphoinositide phosphatase. No cure exists and very few pharmacological avenues are being explored. Here, we treated Mtm1-null mice with tamoxifen (TAM), a drug that modulates estrogen actions and that we have shown earlier to be efficacious in dystrophic (mdx5Cv) mice, a ...
Source: Neuromuscular Disorders - September 10, 2017 Category: Neurology Authors: E. Gayi, H. Ismail, B. Cowling, L. Neff, J. Laporte, L. Scapozza, O. Dorchies Source Type: research
Novel TNNT1 mutation and mild nemaline myopathy phenotype in an Italian patient
Respiratory failure manifests relatively late in the course of many muscle disorders, generally after a severe and generalized muscle weakness has taken place. When it occurs early in a neuromuscular patient, amyotrophic lateral sclerosis and myasthenia gravis are the most frequent conditions. Alternatively, few muscle disorders can be considered, such as late-onset Pompe disease, myotonic dystrophy type 1, myofibrillar myopathies, hereditary myopathy with early respiratory failure associated with mutations of titin gene and congenital myopathies, such as MTM1-related myotubular myopathy, RYR1- and DNM2-related myopathies ...
Source: Neuromuscular Disorders - March 5, 2021 Category: Neurology Authors: Antonio Petrucci, Guido Primiano, Marco Savarese, Cristina Sancricca, Bjarne Udd, Serenella Servidei Source Type: research
The kalaemic and neuromuscular effects of succinylcholine in centronuclear myopathy: A pilot investigation in a canine model
We examined the kalaemic and neuromuscular effects of succinylcholine in dogs with and without autosomal-recessive CNM.
DESIGN: A prospective, experimental study.
SETTING: Anaesthesiology laboratory, College of Veterinary Medicine, Cornell University, New York, USA.
PATIENTS: Six dogs with autosomal-recessive CNM and six control dogs.
INTERVENTIONS: Dogs received succinylcholine 0.3 mg kg−1 during isoflurane anaesthesia.
MAIN OUTCOME MEASURES: Whole blood potassium concentration was measured 5 min before and after succinylcholine administration. Neuromuscular function was measured with acceleromyography and single ...
Source: European Journal of Anaesthesiology - September 2, 2015 Category: Anesthesiology Tags: Neuromuscular blocking agents Source Type: research
MTM1-related myopathy carrier females manifest significant skeletal asymmetries and a spectrum of muscle involvement
X-linked myotubular myopathy (XLMTM) results from mutations in MTM1 and manifests in males with severe congenital hypotonia, weakness and respiratory insufficiency. Carrier females are less well-characterized, with reports indicating a spectrum of disease, ranging from mild facial weakness to severe congenital weakness. We deeply phenotyped a cohort of ten females with causative mutations in MTM1, evaluating the severity of disease expression based on muscle weakness, pulmonary function (spirometry and dynamic breathing MRI), muscle imaging (ultrasound and MRI) and skeletal morphology.
Source: Neuromuscular Disorders - September 10, 2016 Category: Neurology Authors: A. Reghan Foley, B. Cocanougher, L. Flynn, P. Yun, M. Jain, M. Waite, R. Vasavada, S. de Chastonay, S. Donkervoort, C. Bonnemann Source Type: research
Antisense oligonucleotide-mediated Dnm2 knockdown delays myotubular myopathy in mice after a single injection
Centronuclear myopathies (CNM) are non-dystrophic muscle diseases for which no effective therapy is currently available. The most severe form, X-linked CNM, is caused by myotubularin 1 (MTM1) loss-of-function mutations, while the main autosomal dominant form is due to dynamin2 (DNM2) mutations. We previously showed that genetic reduction of DNM2 expression in Mtm1 knockout (Mtm1KO) mice prevents development of muscle pathology. Most recently we have shown that weekly systemic delivery of Dnm2 antisense oligonucleotides (ASOs) into Mtm1KO mice efficiently reduces DNM2 protein level in muscle and prevents the myopathy from developing.
Source: Neuromuscular Disorders - September 10, 2017 Category: Neurology Authors: S. Buono, C. Kretz, C. Koch, A. Rob é, S. Guo, B. Monia, J. Laporte, L. Thielemans, B. Cowling Source Type: research
A multicenter, retrospective medical record review of patients with X-Linked Myotubular myopathy (XLMTM): the RECENSUS study
We examined disease burden and unmet medical need in patients with XLMTM from the RECENSUS study. RECENSUS is an ongoing, multicenter, retrospective chart review of male patients with XLMTM. Data reported here were collected from Sept. 10, 2014 to Jun. 16, 2016 from 6 international sites. Data collection was standardized across sites, performed by trained data extractors, and included demographics, diagnosis, gestation, pulmonary function, hospitalizations, surgeries, motor function, and more.
Source: Neuromuscular Disorders - September 10, 2017 Category: Neurology Authors: A. Beggs, B. Byrne, S. de Chastonay, T. Haselkorn, I. Hughes, E. James, N. Kuntz, J. Simon, L. Swanson, M. Yang, Z. Yu, S. Yum, S. Prasad Source Type: research
Non-compaction cardiomyopathy and early respiratory failure in an adult symptomatic female carrier of centronuclear myopathy caused by a MTM1 mutation
X-linked myotubular myopathy (XLMTM) is a rare neuromuscular condition caused by mutations in the MTM1 gene. Affected males typically present with neonatal hypotonia and weakness, associated with severe morbidities and early death.1,2 Female carriers are believed to be usually asymptomatic; nevertheless, recent reports3,4 have displayed a wide a spectrum of clinical involvement in females that suggesting that MTM1 mutations might be underestimated in this population. Diagnostic clues include generalized weakness, with a noteworthy asymmetric involvement, a variable decline in respiratory function and/or facial weakness and...
Source: Neuromuscular Disorders - August 13, 2018 Category: Neurology Authors: J. Garc ía-García, M.A. Fernández-García, P. Blanco-Arias, M.I. Díaz-Maroto-Cicuendez, F. Salmerón-Martínez, V.M. Hidalgo-Olivares, M. Olivé Source Type: research
O.06 Long term outcomes for X-Linked myotubular Myopathy (XLMTM) with gene replacement therapy, resamirigene bilparvovec: Preliminary results from ASPIRO
ASPIRO (NCT03199469) is a first-in-human clinical study of resamirigene bilparvovec (AT132), an AAV-mediated, muscle-directed gene replacement therapy in boys with ventilator-dependent XLMTM, a devastating congenital myopathy. We previously reported study outcomes through 48 weeks following dosing, including 4 participants with treatment-related, fatal, hepatobiliary toxicity. Here we report long-term outcomes among the 20 surviving dosed participants (new data cut of 01MAR2022): n=6 at 1.3 x 1014 vg/kg AT132, (dosing age, median 0.9 [range, 0.8 –4.1] years; post-dose follow-up period age, 4.1 [3.9–4.4] years); n=14 at...
Source: Neuromuscular Disorders - October 1, 2022 Category: Neurology Authors: P. Shieh, N. Kuntz, J. Dowling, W. M üller-Felber, A. Blaschek, C. Bönnemann, R. Foley, D. Saade, A. Seferian, L. Servais, A. Bowden, M. Sarazen, J. Coats, N. Lakshman, C. Han, S. Prasad, S. Rico, W. Miller Source Type: research
Potassium dependent rescue of a myopathy with core-like structures in mouse
In this study, we identify a mouse RyR1 model in which heterozygous animals display clinical and pathological hallmarks of myopathy with core-like structures. The RyR1 mutation decreases sensitivity to activated calcium release and myoplasmic calcium levels, subsequently affecting mitochondrial calcium and ATP production. Mutant muscle shows a persistent potassium leak and disrupted expression of regulators of potassium homeostasis. Inhibition of KATP channels or increasing interstitial potassium by diet or FDA-approved drugs can reverse the muscle weakness, fatigue-like physiology and pathology. We identify regulators of ...
Source: eLife - January 7, 2015 Category: Biomedical Science Tags: Cell Biology congenital myopathy Human KATP channel Mouse potassium homeostasis ryanodine receptor Source Type: research
PCSK9 Inhibitors May Lower Cholesterol in Patients with Statin-Associated Immune-Mediated Necrotizing Myopathy
A 2019 study demonstrated the benefit of a newer drug class, PCSK9 inhibitors, to help lower cholesterol in patients with statin-associated immune-mediated necrotizing myopathy...
Source: The Rheumatologist - September 23, 2020 Category: Rheumatology Authors: Vanessa Caceres Tags: Drug Updates Arthritis & Rheumatology cholesterol immune-mediated necrotizing myopathy PCSK9 inhibitors protein convertase subtilisin/kexin type 9 inhibitors statin-associated myopathy Source Type: research
Nebulin (NEB) mutations in a childhood onset distal myopathy with rods and cores uncovered by next generation sequencing
th
& Francesco Muntoni
Source: European Journal of Human Genetics - February 27, 2013 Category: Genetics & Stem Cells Authors: Mariacristina ScotoThomas CullupSebahattin CirakShu YauAdnan Y ManzurLucy FengThomas S JacquesGlenn AndersonStephen AbbsCaroline SewryHeinz JungbluthFrancesco Muntoni Tags: nebulin distal myopathy next generation sequencing Source Type: research
Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations
Zohar Argov
& Anders Oldfors
Source: European Journal of Human Genetics - November 6, 2013 Category: Genetics & Stem Cells Authors: Homa TajsharghiSimon HammansChristopher LindbergAlexander LossosNigel F ClarkeIngrid MazantiLeigh B WaddellYakov FelligNicola FouldsHaider KatifiRichard WebsterOlayinka RaheemBjarne UddZohar ArgovAnders Oldfors Tags: Myosin heavy chain MYH2 ophthalmoplegia myosin myopathy Source Type: research
Deleterious mutation in FDX1L gene is associated with a novel mitochondrial muscle myopathy
Feuk
& Orly Elpeleg
Source: European Journal of Human Genetics - November 27, 2013 Category: Genetics & Stem Cells Authors: Ronen SpiegelAnn SaadaJonatan HalvardsonDevorah SoifermanAvraham ShaagSimon EdvardsonYoseph HorovitzMorad KhayatStavit A ShalevLars FeukOrly Elpeleg Tags: FDX1L gene Fe-S cluster respiratory chain metabolic myopathy Source Type: research
