scholarly journals Special Issue: Pathophysiology and Therapeutic Perspectives in DMD: The Well-Defined Role of the Immune System

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1911
Author(s):  
Andrea Farini
Keyword(s):  
Immune System ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Wasting ◽  
Special Issue ◽  
Wasting Disease ◽  
Muscle Wasting Disease

Duchenne muscular dystrophy (DMD) is the most common, lethal, muscle-wasting disease of childhood [...]

scholarly journals From diagnosis to therapy in Duchenne muscular dystrophy

2020 ◽  
Vol 48 (3) ◽  
pp. 813-821 ◽  
Author(s):  
Arran Babbs ◽  
Maria Chatzopoulou ◽  
Ben Edwards ◽  
Sarah E. Squire ◽  
Isabel V.L. Wilkinson ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Wasting ◽  
Exon Skipping ◽  
Short Review ◽  
Current Status ◽  
Muscle Membrane ◽  
Therapeutic Approaches ◽  
Wasting Disease ◽  
Muscle Wasting Disease

Genetic approaches for the diagnosis and treatment of inherited muscle diseases have advanced rapidly in recent years. Many of the advances have occurred in the treatment of Duchenne muscular dystrophy (DMD), a muscle wasting disease where affected boys are typically wheelchair bound by age 12 years and generally die in their twenties from respiratory failure or cardiomyopathy. Dystrophin is a 421 kD protein which links F-actin to the extracellular matrix via the dystrophin-associated protein complex (DAPC) at the muscle membrane. In the absence of dystrophin, the DAPC is lost, making the muscle membrane more susceptible to contraction-induced injury. The identification of the gene causing DMD in 1986 resulted in improved diagnosis of the disease and the identification of hotspots for mutation. There is currently no effective treatment. However, there are several promising genetic therapeutic approaches at the preclinical stage or in clinical trials including read-through of stop codons, exon skipping, delivery of dystrophin minigenes and the modulation of expression of the dystrophin related protein, utrophin. In spite of significant progress, the problem of targeting all muscles, including diaphragm and heart at sufficiently high levels, remains a challenge. Any therapy also needs to consider the immune response and some treatments are mutation specific and therefore limited to a subgroup of patients. This short review provides a summary of the current status of DMD therapy with a particular focus on those genetic strategies that have been taken to the clinic.

scholarly journals Abnormal Calcium Handling in Duchenne Muscular Dystrophy: Mechanisms and Potential Therapies

2021 ◽  
Vol 12 ◽  
Author(s):  
Satvik Mareedu ◽  
Emily D. Million ◽  
Dongsheng Duan ◽  
Gopal J. Babu
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Therapeutic Strategy ◽  
Muscle Wasting ◽  
Premature Death ◽  
Calcium Handling ◽  
Muscle Degeneration ◽  
Wasting Disease ◽  
Fatty Replacement ◽  
Muscle Wasting Disease

Duchenne muscular dystrophy (DMD) is an X-linked muscle-wasting disease caused by the loss of dystrophin. DMD is associated with muscle degeneration, necrosis, inflammation, fatty replacement, and fibrosis, resulting in muscle weakness, respiratory and cardiac failure, and premature death. There is no curative treatment. Investigations on disease-causing mechanisms offer an opportunity to identify new therapeutic targets to treat DMD. An abnormal elevation of the intracellular calcium (Cai2+) concentration in the dystrophin-deficient muscle is a major secondary event, which contributes to disease progression in DMD. Emerging studies have suggested that targeting Ca2+-handling proteins and/or mechanisms could be a promising therapeutic strategy for DMD. Here, we provide an updated overview of the mechanistic roles the sarcolemma, sarcoplasmic/endoplasmic reticulum, and mitochondria play in the abnormal and sustained elevation of Cai2+ levels and their involvement in DMD pathogenesis. We also discuss current approaches aimed at restoring Ca2+ homeostasis as potential therapies for DMD.

Ayurvedic management of Ducchen’s Muscular Dystrophy - A Case report

2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Jayaraj R. ◽  
Veena G. Rao ◽  
Jyothi Nagalikar
Keyword(s):  
Muscular Dystrophy ◽  
Cardiac Dysfunction ◽  
Muscle Wasting ◽  
Progressive Disease ◽  
Genetic Disorder ◽  
Dystrophin Gene ◽  
Wasting Disease ◽  
Number Of Patients ◽  
Choice Of Treatment ◽  
Muscle Wasting Disease

Ducchen’s muscular dystrophy is most common X-linked recessive disorder affecting 30 in 100,000 live male births. The primary cause of this disease is mutations in Dystrophin gene which is essential for the structural and functional integrity of muscle. It is a progressive muscle wasting disease in which patients frequently develop contractures and lose the ability to walk between 6 and 12 years of age. With progressive disease most patients succumb to death from respiratory failure and cardiac dysfunction in their twenties. As this is a genetic disorder we can consider it as Adibala Pravritta Vyadhi. As Mamsa Kshaya is seen at some muscles and Mamsa Vriddhi at other this is an Avarana Vata Vyadhi. In both Upsthambha and Nirupasthmbha Vatavyadhi, Basthi is considered as prime choice of treatment. A Variety of Ksheerabasti in the form of Kalabasti is studied in this condition by taking subjective and objective parameters. As this has given better improvement with no adverse effects in the patient, it can be tried in large number of patients.

scholarly journals Donnan dominated ion homeostasis and the longevity of ischemic Na+-loaded dystrophic skeletal muscle

2020 ◽  
Author(s):  
Catherine E Morris ◽  
Joshua J Wheeler ◽  
Béla Joos
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscle Wasting ◽  
Low Cost ◽  
Ion Homeostasis ◽  
Feedback Process ◽  
Chloride Permeability ◽  
Wasting Disease ◽  
Sodium Permeability ◽  
Muscle Wasting Disease

ABSTRACTThe inherited muscle-wasting disease, Duchenne muscular dystrophy (DMD), renders skeletal muscle fibers (SMFs) Na+-overloaded, ischemic, membrane-damaged, cation-leaky, depolarized, and prone to myogenic firing. DMD fibers nevertheless survive up to 3 decades before succumbing to Ca2+-necrosis. The Ca2+-necrosis is explicable, the longevity is not. Modeling here shows that SMFs’ ion homeostasis strategy, a low-cost resilient Pump-Leak/Donnan feedback process we term “Donnan dominated”, underpins that longevity. Together, SMFs’ huge chloride-permeability and tiny sodium-permeability minimize excitability and pump costs, facilitating the outsized SMF pump-reserve that lets DMD fibers withstand deep ischemia and leaky channels. We illustrate how, as these impairments intensify, patients’ chronic Na+-overload (now non-invasively evident via Na23-MRI) would change. In simulations, prolonged excitation (→physiological Na+-overloading) and/or intense ischemia (→too little Na+-pumping) and accumulated bleb-damage (→too much Na+-leaking) eventually trigger Ca2+-overloading conditions. Our analysis implies an urgent need to identify SMFs’ pivotal small PNa, thereby opening new therapeutic remediation routes.

scholarly journals Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program

2015 ◽  
Vol 112 (49) ◽  
pp. E6780-E6789 ◽  
Author(s):  
Alexander Morrison-Nozik ◽  
Priti Anand ◽  
Han Zhu ◽  
Qiming Duan ◽  
Mohamad Sabeh ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Atrophy ◽  
Muscle Performance ◽  
Therapeutic Effects ◽  
Wasting Disease ◽  
As Doping ◽  
Ergogenic Effects ◽  
Muscle Wasting Disease ◽  
Direct Induction

Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular basis underlying these performance-enhancing properties of GCs in skeletal muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are mediated by direct induction of the metabolic transcription factor KLF15, defining a downstream pathway distinct from that resulting in GC-related muscle atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic severity and muscle GC–KLF15 signaling mediates salutary therapeutic effects in the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated transactivation is often associated with muscle atrophy and other adverse effects of pharmacologic GC administration, our data define a distinct GR-induced gene regulatory pathway that contributes to therapeutic effects of GCs in DMD through proergogenic metabolic programming.

Have Duchenne Muscular Dystrophy Patients an Increased Cancer Risk?

2021 ◽  
pp. 1-5
Author(s):  
Gian Luca Vita ◽  
Luisa Politano ◽  
Angela Berardinelli ◽  
Giuseppe Vita
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Systematic Investigation ◽  
Mdx Mice ◽  
True Incidence ◽  
Patients With Cancer ◽  
Dmd Gene ◽  
Age Range ◽  
Prevalence Of Cancer

Background: Increasing evidence suggests that Duchenne muscular dystrophy (DMD) gene is involved in the occurrence of different types of cancer. Moreover, development of sarcomas was reported in mdx mice, the murine model of DMD, in older age. So far, nine isolated DMD patients were reported with concomitant cancer, four of whom with rhabdomyosarcoma (RMS), but no systematic investigation was performed about the true incidence of cancer in DMD. Methods: All members of the Italian Association of Myology were asked about the occurrence of cancer in their DMD patients in the last 30 years. Results: Four DMD patients with cancer were reported after checking 2455 medical records. One developed brain tumour at the age of 35 years. Two patients had alveolar RMS at 14 and 17 years of age. The fourth patient had a benign enchondroma when 11-year-old. Conclusion: Prevalence of cancer in general in the Italian DMD patients does not seem to be different from that in the general population with the same age range. Although the small numbers herein presented do not allow definitive conclusion, the frequent occurrence of RMS in DMD patients raises an alert for basic researchers and clinicians. The role of DMD gene in cancer merits further investigations.

scholarly journals Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models

2019 ◽  
Vol 8 ◽  
pp. 204800401987958
Author(s):  
HR Spaulding ◽  
C Ballmann ◽  
JC Quindry ◽  
MB Hudson ◽  
JT Selsby
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Mdx Mice ◽  
Dystrophin Deficiency ◽  
Muscle Wasting Disease ◽  
Dystrophin Protein

Background Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autophagy in cardiac muscle. We hypothesized that with disease progression autophagy would become increasingly dysfunctional based upon indirect autophagic markers. Methods Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. Results Counter to our hypothesis, markers of autophagy were similar between groups. Given these surprising results, two independent experiments were conducted using 14-month-old mdx mice or 10-month-old mdx/Utrn± mice, a more severe model of Duchenne muscular dystrophy. Data from these animals suggest increased autophagosome degradation. Conclusion Together these data suggest that autophagy is not impaired in the dystrophic myocardium as it is in dystrophic skeletal muscle and that disease progression and related injury is independent of autophagic dysfunction.

Muscle wasting and carbohydrate homeostasis in Duchenne muscular dystrophy

Neurology ◽  
1978 ◽  
Vol 28 (12) ◽  
pp. 1224-1224 ◽  
Author(s):  
M. W. Haymond ◽  
K. E. Strobel ◽  
D. C. DeVivo
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Wasting ◽  
Carbohydrate Homeostasis

scholarly journals ROLE OF PANCHAKARMA IN DUCHENNE MUSCULAR DYSTROPHY

2013 ◽  
Vol 4 (2) ◽  
pp. 272-275
Author(s):  
Ashutosh Chaturvedi ◽  
Prasanna N Rao ◽  
Shailaja U ◽  
M Ashvini Kumar
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy

scholarly journals The microRNA, miR-133b, functions to slow Duchenne muscular dystrophy pathogenesis

2020 ◽  
Author(s):  
Thomas Taetzsch ◽  
Dillon Shapiro ◽  
Randa Eldosougi ◽  
Tracey Myers ◽  
Robert Settlage ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Skeletal Muscles ◽  
Tibialis Anterior Muscle ◽  
Muscle Fibers ◽  
Progressive Degeneration ◽  
Protein Encoding ◽  
Small Muscle ◽  
Encoding Genes

AbstractDuchenne muscular dystrophy (DMD) is characterized by progressive degeneration of skeletal muscles. To date, there are no treatments available to slow or prevent the disease. Hence, it remains essential to identify molecular factors that promote muscle biogenesis since they could serve as therapeutic targets for treating DMD. While the muscle enriched microRNA, miR-133b, has been implicated in the biogenesis of muscle fibers, its role in DMD remains unknown. To assess the role of miR-133b in DMD-affected skeletal muscles, we genetically ablated miR-133b in the mdx mouse model of DMD. In the absence of miR-133b, the tibialis anterior muscle of juvenile and adult mdx mice is populated by small muscle fibers with centralized nuclei, exhibits increased fibrosis, and thickened interstitial space. Additional analysis revealed that loss of miR-133b exacerbates DMD-pathogenesis partly by altering the number of satellite cells and levels of protein-encoding genes, including previously identified miR-133b targets as well as genes involved in cell proliferation and fibrosis. Altogether, our data demonstrate that skeletal muscles utilize miR-133b to mitigate the deleterious effects of DMD.

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