Myology research highlights
RSS feedImproved dystrophic pathology using a second-generation utrophin modulator
DMD is a lethal, X-linked muscle-wasting disease caused by lack of the cytoskeletal protein dystrophin. There is currently no cure for DMD although various promising approaches are progressing through human clinical trials. By pharmacologically modulating the expression of the dystrophin-related protein utrophin, the authors have previously demonstrated in dystrophin deficient mdx studies, daily SMT C1100 … [Read more]
In vivo rescue of dysferlin protein by SmaRT
The modification of the pre-mRNA cis-splicing process employing a pre-mRNA trans-splicing molecule (PTM) is an attractive strategy for the in situ correction of genes whose careful transcription regulation and full-length expression is determinative for protein function, as it is the case for the dysferlin (DYSF, Dysf) gene. Loss-of-function mutations of DYSF result in different types … [Read more]
Physiological consequences of different levels of dystrophin in the mdx mouse
Splice modulation therapy has shown great clinical promise in Duchenne muscular dystrophy, resulting in the production of dystrophin protein. Despite this, the relationship between restoring dystrophin to established dystrophic muscle and its ability to induce clinically relevant changes in muscle function is poorly understood. In order to robustly evaluate functional improvement, this study used in … [Read more]
Astrocytes contribute to the severity of spinal muscular atrophy
Systemically low levels of survival motor neuron-1 (SMN1) protein cause spinal muscular atrophy (SMA). α-motor neurons of the spinal cord are considered particularly vulnerable in this genetic disorder, and their dysfunction and loss cause progressive muscle weakness, paralysis, and eventually premature death of afflicted individuals. Historically, SMA was therefore considered a motor neuron-autonomous disease. However, … [Read more]
Development and validation of a functional scale for spinal and bulbar muscular atrophy
This study aimed to develop, validate, and evaluate a disease-specific outcome measure for SBMA: the Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS). The authors examined the Japanese version (SBMAFRS-J) in 80 Japanese SBMA subjects to evaluate its validity and reliability. They then assessed this scale longitudinally in 41 additional SBMA subjects. The English … [Read more]
Development of a functional composite score for SMA
The objective of this study was to construct a composite score of global function that will discriminate among people with Spinal Muscular Atrophy (SMA). Data were collected from 126 participants with SMA Types 2 and 3. Scores from the Hammersmith Functional Motor Scale-Expanded and Upper Limb Module were expressed as a percentage of the maximum … [Read more]
Mitochondrial dysfunction reveals the role of mRNA poly(a) tail regulation in oculopharyngeal muscular dystrophy pathogenesis
Oculopharyngeal muscular dystrophy (OPMD), a late-onset disorder characterized by progressive degeneration of specific muscles, results from the extension of a polyalanine tract in poly(A) binding protein nuclear 1 (PABPN1). While the roles of PABPN1 in nuclear polyadenylation and regulation of alternative poly(A) site choice are established, the molecular mechanisms behind OPMD remain undetermined. Here, we … [Read more]
Oral fructose ingestion improves exercise tolerance in glycogen storage disease type IIIa
Glycogen storage disease type IIIa (GSDIIIa) is classically regarded as a glycogenosis with fixed weakness. However, the authors of the present study hypothesized that exercise intolerance in GSDIIIa is related to muscle energy failure and that oral fructose ingestion could improve exercise tolerance in this metabolic myopathy. They challenged metabolism with cycle-ergometer exercise and measured … [Read more]
X-linked myopathy with excessive autophagy does not affect cardiac muscle
In X-linked myopathy with excessive autophagy (XMEA) progressive sarcoplasmic accumulation of autolysosomes filled with undegraded debris leads to atrophy and weakness of skeletal muscles. XMEA is caused by compromised acidification of lysosomes resulting from hypofunction of the proton pump vacuolar ATPase (V-ATPase), due to hypomorphic mutations in VMA21, whose protein product assembles V-ATPase. To what … [Read more]
Use of muscle MRI to diagnose X-linked myopathy with excessive autophagy
X-linked myopathy with excessive autophagy (XMEA) is an X-linked recessive myopathy due to recently reported mutations in the VMA21 gene. In this study, four men from 2 separate families were studied. The clinical presentation, genetic data, muscle biopsy, and muscle MRI were analyzed. A known VMA21 mutation c.163 + 4A>G and a new mutation c.163 + 3A>G, respectively were … [Read more]
