Muscular dystrophy

This case report provides insights into the physiotherapy management of a 12-year-old male with Duchenne muscular dystrophy (DMD). DMD is a devastating genetic disorder characterized by progressive muscle degeneration and weakness. Skeletal muscle degeneration is induced by a genetic disorder. It is a common X-linked condition that causes hypertrophy of the calves and proximal muscular weakness in children. It frequently results in early mortality, wheelchair confinement, and delays in motor development...

DNAJB6b is a molecular chaperone of the heat shock protein network, shown to play a crucial role in preventing aggregation of several disease-related intrinsically disordered proteins. Using homology modeling and microsecond-long all-atom molecular dynamics (MD) simulations, we show that monomeric DNAJB6b is a transiently interconverting protein cycling between three states: a closed state, an open state (both abundant), and a less abundant extended state. Interestingly, the reported regulatory autoinhibitory anchor between helix V in the G/F1 region and helices II/III of the J-domain, which obstructs the access of Hsp70 to the J-domain remains present in all three states...

BACKGROUND: As one of the most common congenital abnormalities in male births, cryptorchidism has been found to have a polygenic aetiology according to previous studies of common variants. However, little is known about genetic predisposition of rare variants for cryptorchidism, since rare variants have larger effective size on diseases than common variants. METHODS: In this study, a cohort of 115 Chinese probands with cryptorchidism was analysed using whole-genome sequencing, alongside 19 parental controls and 2136 unaffected men...

Mutations in DNAJB6 are a well-established cause of limb girdle muscular dystrophy type D1 (LGMD D1). Patients with LGMD D1 develop progressive muscle weakness with histology showing fibre damage, autophagic vacuoles, and aggregates. Whilst there are many reports of LGMD D1 patients, the role of DNAJB6 in the muscle is still unclear. In this study, we developed a loss of function zebrafish model in order to investigate the role of Dnajb6. Using a double dnajb6a and dnajb6b mutant model, we show that loss of Dnajb6 leads to a late onset muscle weakness...

Skeletal muscle's regenerative ability is vital for maintaining muscle function, but chronic diseases like Duchenne muscular dystrophy can deplete this capacity. Muscle satellite cells, quiescent in normal situations, are activated during muscle injury, expressing myogenic regulatory factors, and producing myogenic progenitor cells. It was reported that muscle stem cells in primary culture and reserve cells in C2C12 cells express anti-apoptotic protein Bcl-2. Although the role of Bcl-2 expressed in myogenic cells has been thought to be to enhance cell viability, we hypothesized that Bcl-2 may promote the formation of reserve cells...

Collagen VI-related dystrophies (COL6-RDs) are a group of severe, congenital-onset muscular dystrophies for which there is no effective causative treatment. Dominant-negative mutations are common in COL6A1 , COL6A2 , and COL6A 3 genes, encoding the collagen α1, α2, and α3 (VI) chains. They act by incorporating into the hierarchical assembly of the three α (VI) chains and consequently produce a dysfunctional collagen VI extracellular matrix, while haploinsufficiency for any of the COL6 genes is not associated with disease...

Dysferlin is a 237 kDa membrane-associated protein characterised by multiple C2 domains with a diverse role in skeletal and cardiac muscle physiology. Mutations in DYSF are known to cause various types of human muscular dystrophies, known collectively as dysferlinopathies, with some patients developing cardiomyopathy. A myriad of in vitro membrane repair studies suggest that dysferlin plays an integral role in the membrane repair complex in skeletal muscle. In comparison, less is known about dysferlin in the heart, but mounting evidence suggests that dysferlin's role is similar in both muscle types...

BACKGROUND: X-linked dystrophin-deficient muscular dystrophy (MD) is a form of MD caused by variants in the DMD gene. It is a fatal disease characterized by progressive weakness and degeneration of skeletal muscles. HYPOTHESIS/OBJECTIVES: Identify deleterious genetic variants in DMD by whole-genome sequencing (WGS) using a next-generation sequencer. ANIMALS: One MD-affected cat, its parents, and 354 cats from a breeding colony. METHODS: We compared the WGS data of the affected cat with data available in the National Center for Biotechnology Information database and searched for candidate high-impact variants by in silico analyses...

Background: Quantitative muscle MRI (qMRI) is a promising tool for evaluating and monitoring neuromuscular disorders (NMD). However, the application of different imaging protocols and processing pipelines restricts comparison between patient cohorts and disorders. In this qMRI study, we aim to compare dystrophic (limb-girdle muscular dystrophy), inflammatory (inclusion body myositis), and metabolic myopathy (Pompe disease) as well as patients with post-COVID-19 conditions suffering from myalgia to healthy controls...

The study aimed to provide quantitative information on the utilization of MRI transverse relaxation time constant (MRI-T2 ) of leg muscles in DMD clinical trials by developing multivariate disease progression models of Duchenne muscular dystrophy (DMD) using 6-min walk distance (6MWD) and MRI-T2 . Clinical data were collected from the prospective and longitudinal ImagingNMD study. Disease progression models were developed by a nonlinear mixed-effect modeling approach. Univariate models of 6MWD and MRI-T2 of five muscles were developed separately...

BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare, degenerative, recessive X-linked neuromuscular disease. Mutations in the gene encoding dystrophin lead to the absence of functional dystrophin protein. Individuals living with DMD exhibit progressive muscle weakness resulting in loss of ambulation and limb function, respiratory insufficiency, and cardiomyopathy, with multiorgan involvement. Adeno-associated virus vector-mediated gene therapy designed to enable production of functional dystrophin protein is a new therapeutic strategy...

BACKGROUND: Duchenne muscular dystrophy (DMD) is a devastating X-linked muscle disease. Clinical evaluation of DMD uses patient-intensive motor function tests, and the recent development of wearable devices allows the collection of a variety of biometric information, including physical activity. OBJECTIVE: In this study, we examined differences in physical activity and heart rate variability (HRV) between patients with DMD and healthy subjects using a wearable device, and investigated any association between these parameters and motor function in patients with DMD...

Cell therapies derived from induced pluripotent stem cells (iPSCs) offer a promising avenue in the field of regenerative medicine due to iPSCs' expandability, immune compatibility, and pluripotent potential. An increasing number of preclinical and clinical trials have been carried out, exploring the application of iPSC-based therapies for challenging diseases, such as muscular dystrophies. The unique syncytial nature of skeletal muscle allows stem/progenitor cells to integrate, forming new myonuclei and restoring the expression of genes affected by myopathies...

Duchenne muscular dystrophy (DMD) is a genetic progressive muscle-wasting disorder that leads to rapid loss of mobility and premature death. The absence of functional dystrophin in DMD patients reduces sarcolemma stiffness and increases contraction damage, triggering a cascade of events leading to muscle cell degeneration, chronic inflammation, and deposition of fibrotic and adipose tissue. Efforts in the last decade have led to the clinical approval of novel drugs for DMD that aim to restore dystrophin function...

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Skeletal muscle, comprising a significant proportion (40 to 50 percent) of total body weight in humans, plays a critical role in maintaining normal physiological conditions. Muscle atrophy occurs when the rate of protein degradation exceeds protein synthesis. Sarcopenia refers to age-related muscle atrophy, while cachexia represents a more complex form of muscle wasting associated with various diseases such as cancer, heart failure, and AIDS. Recent research has highlighted the involvement of signaling pathways, including IGF1-Akt-mTOR, MuRF1-MAFbx, and FOXO, in regulating the delicate balance between muscle protein synthesis and breakdown...

Duchenne muscular dystrophy (DMD) is a devastating monogenic skeletal muscle wasting disorder. While many pharmacological and genetic interventions have been reported in preclinical studies, few have progressed to clinical trials with meaningful benefit. Identifying therapeutic potential may be limited by availability of suitable preclinical mouse models. More rigorous testing across models with varied background strains and mutations may identify treatments for clinical success. Here we report the generation of a DMD mouse model, with a CRISPR-induced deletion within exon 62 of the Dmd gene, and the first generated in BALB/c mice...

Xenografts of human skeletal muscle generated in mice can be used to study muscle pathology and to test drugs designed to treat myopathies and muscular dystrophies for their efficacy and specificity in human tissue. We previously developed methods to generate mature human skeletal muscles in immunocompromised mice starting with human myogenic precursor cells (hMPCs) from healthy individuals and individuals with facioscapulohumeral muscular dystrophy (FSHD). Here, we examine a series of alternative treatments at each stage in order to optimize engraftment...

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is a rare inherited neuromuscular disease. At first, cardiac involvement may be asymptomatic. Therefore, assessing patients using non-invasive methods can help detect any changes. OBJECTIVES: Analyze the electrocardiogram (ECG) test and heart rate variability (HRV) of the DMD group and compare the information with that of the age-matched control group. METHODS: A prospective study with 27 male patients with DMD (11...

Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration, with respiratory and cardiac complications, caused by mutations in the DMD gene, encoding the protein dystrophin. Various DMD mutations result in different phenotypes and disease severity. Understanding genotype/phenotype correlations is essential to optimize clinical care, as mutation-specific therapies and innovative therapeutic approaches are becoming available. Disease modifier genes, trans-active variants influencing disease severity and phenotypic expressivity, may modulate the response to therapy, and become new therapeutic targets...