Blog Archives
Off-label use of Ataluren in non-ambulatory nmDMD patients
About 15% of Duchenne muscular dystrophy (DMD) cases are caused by point mutations leading to premature stop codons and disrupted synthesis of the dystrophin protein. Following positive results in ambulatory nmDMD (non-sense mutation Duchenne muscular dystrophy) patients, Ataluren (Translarna® by PTC Therapeutics) received conditional approval in ambulant nmDMD patients. However, there are limited data on … [Read more]
Micro-utrophin improves cardiac and skeletal muscle pathology in D2/mdx mice
There is currently no effective treatment except palliative care for Duchenne muscular dystrophy (DMD), although personalized treatments such as exon skipping, stop codon read-through, and viral-based gene therapies are making progress. Patients present with skeletal muscle pathology, but most also show cardiomyopathy by the age of 10. A systemic therapeutic approach is needed that treats … [Read more]
Is the 2-minute walk test an effective alternative to a 6-minute walk test?
Functional tests such as Motor Function Measure-32 (MFM-32), supine to stand, ascend/descend stairs permit the assessment of task-specific motor function in neuromuscular disease (NMD). The 6-min walk test (6MWT), though functional, is primarily used to assess endurance and disease progression in children with neuromuscular disorders. Barriers to 6MWT administration, in this population, can include reduced … [Read more]
ALS and SMA are linked via the ASC-1 complex
Understanding the molecular pathways disrupted in motor neuron diseases is urgently needed. Here, the authors employed CRISPR knockout (KO) to investigate the functions of four ALS-causative RNA/DNA binding proteins (FUS, EWSR1, TAF15 and MATR3) within the RNAP II/U1 snRNP machinery. They found that each of these structurally related proteins has distinct roles with FUS KO … [Read more]
Seronegative IMNM: a subgroup with distinctive features from seropositive IMNM
A majority of patients with immune-mediated necrotizing myopathy (IMNM)—a relatively new entity within the spectrum of idiopathic inflammatory myopathies (IIMs)—suffer from disability despite treatment, indicating inadequate management. Here, the authors conducted a cross-sectional study to investigate clinical and serologic characteristics in a case series of IMNM, including seronegative IMNM, diagnosed in tertiary referral hospitals in … [Read more]
Whole exome sequencing: a comprehensive and unbiased approach to establish a genetic diagnosis in patients with a likely mitochondrial disorder
Mitochondrial disorders, characterized by clinical symptoms and/or OXPHOS deficiencies, are caused by pathogenic variants in mitochondrial genes. However, pathogenic variants in some of these genes can lead to clinical manifestations which overlap with other neuromuscular diseases, which can be caused by pathogenic variants in non-mitochondrial genes as well. Mitochondrial pathogenic variants can be found in … [Read more]
Rapamycin rescues mitochondrial myopathy
The mTOR inhibitor rapamycin ameliorates the clinical and biochemical phenotype of mouse, worm, and cellular models of mitochondrial disease, via an unclear mechanism. Here, the authors show that prolonged rapamycin treatment improved motor endurance, corrected morphological abnormalities of muscle, and increased cytochrome c oxidase (COX) activity of a muscle-specific Cox15 knockout mouse (Cox15 sm/sm ). … [Read more]
Pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibodies
A form of idiopathic inflammatory myopathy associated with anti-signal recognition particle (SRP) or anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies (aAb) has been individualised and is referred to as immune-mediated necrotising myopathy (IMNM). The level of aAb correlates with IMNM activity and disease may respond to immunosuppression, suggesting that they are pathogenic. This study, xhich also involved clinicians … [Read more]
Xanthine oxidase is hyper-active in DMD
Generation of superoxide by xanthine oxidase can be stimulated under ischemic and aberrant calcium homeostasis. Given that patients and mice with Duchenne muscular dystrophy (DMD) are affected by ischemia and excessive calcium influx, this study tested the hypothesis that xanthine oxidase activity is elevated and contributes to disease pathology. Xanthine oxidase activity was measured by … [Read more]
Reducing dynamin 2 corrects DNM2-related dominant centronuclear myopathy
Centronuclear myopathies (CNM) are a group of severe muscle diseases for which no effective therapy is currently available. The authors of the present study have previously shown that reduction of the large GTPase DNM2 in a mouse model of the X-linked form, due to loss of myotubularin phosphatase MTM1, prevents the development of the skeletal … [Read more]
