Faculty Opinions recommendation of Successful regional delivery and long-term expression of a dystrophin gene in canine muscular dystrophy: a preclinical model for human therapies.

Background: Duchenne Muscular Dystrophy (DMD) is a fatal muscular dystrophy of pediatric population coupled with other secondary comorbidities including mental retardation and neuropsychological impairments. Mutation location in the dystrophin gene, have been associated with neuropsychological functioning in DMD. Purpose: We investigated temporal changes in the neuropsychological functioning of DMD subjects, hitherto understudied. Methods: Subjects with suspected DMD were enrolled according to the ethical guidelines. Genetic confirmation by Multiplex Ligation Dependent Probe Amplification was carried out to identify pathogenic deletion or duplication in dystrophin gene. Intellectual and neuropsychological functioning was assessed by using standardized batteries. Investigated neuropsychological domains included visual, verbal and working memory, selective and sustained attention, executive functioning, verbal fluency, and visuo-constructive and visuo-spatial abilities. The assessments were carried out at baseline and followed for one time point in 30 cases. Result: The follow-up assessment revealed that neuropsychological functioning did not worsen with time. Improvements were seen in block designing task ( p = 0.050), serial positioning primacy effect ( p = 0.002), Stroop incongruent task ( p = 0.006), visual long-term memory ( p = 0.003) and attention ( p = 0.001). DMD cases with mutation location affecting short dystrophin isoform (Dp140) also showed improvement in these domains. Conclusion: No temporal alterations were found in DMD subjects, though improvements in few domains were observed. Neuropsychological rehabilitation may be useful in improving the quality of life in DMD subjects.

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A CASE REPORT ON THE MANAGEMENT OF DUCHENNE’S MUSCULAR DYSTROPHY (DMD) WITH MATRA BASTI

November 2020 - International Ayurvedic Medical Journal ◽

10.46607/iamj15p5022021 ◽

2021 ◽

Vol p5 (02) ◽

pp. 2750-2755

Author(s):

Sharayu Kachole ◽

Niranjan Rao ◽

Padmakiran C

Keyword(s):

Muscular Dystrophy ◽

Treatment Protocol ◽

Dystrophin Gene ◽

Shoulder Girdle ◽

Recessive Mutation ◽

Multiple Systems ◽

Before And After ◽

Dual Action ◽

Duchenne's Muscular Dystrophy

Duchenne’s Muscular Dystrophy (DMD) is the most common x-linked disorder in children presenting in early childhood due to recessive mutation of the dystrophin gene. It is characterized by progressive weak-ness in hip and shoulder girdle muscles beginning by age 5. Although there is no absolute cure for DMD, therapies can delay the onset or slow down the progression of disease. Survival beyond the age of 30 years is rare due to the severe chronic complication involving multiple systems. Serum Creatine Phosphokinase (CPK) level determination is the most specific objective parameter for the diagnosis and assessment of se-verity of Muscular Dystrophy (MD). Based on the presentation of DMD, it can be diagnosed as Mamsavru-ta Vatal leading to Mamsa Dhatu Upashoshana which is the consequence of Beejabhagavikruti. There will be continuous destruction of Dhatu leading to Vataprakopa again. Hence, the line of management is con-trolling the Vata and preventing the destruction. The best treatment for it which has this dual action is Mat-ra Basti. With this basic concept, a male child of 10 years diagnosed as Mamsavruta Vata was treated with Matra Basti using Dhanwantara Taila 10 ml/day for about 9 months. As there was associated Sama Do-shavastha, Agnichikitsa Lepa was advised for 7 days initially. The treatment showed significant reduction in the level of CPK tested before and after the treatment. Hence, the treatment protocol followed can be taken up for further research and can prove with evidence that, it can be effectively practiced in the man-agement of DMD. The long-term benefit, improvement in disease, quality of life can be accessed through the research with long term follow-ups.

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Swiss physicians' practices of long-term mechanical ventilatory support of children and adolescent with Duchenne muscular dystrophy

Neuropediatrics ◽

10.1055/s-2005-867996 ◽

2005 ◽

Vol 36 (02) ◽

Author(s):

GP Ramelli ◽

J Hammer

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Ventilatory Support ◽

Mechanical Ventilatory Support ◽

Children And Adolescent

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

Journal of Ayurveda and Integrated Medical Sciences (JAIMS) ◽

10.21760/jaims.v2i4.9376 ◽

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.

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Dental pulp stem cells can improve muscle dysfunction in animal models of Duchenne muscular dystrophy

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02099-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yuko Nitahara-Kasahara ◽

Mutsuki Kuraoka ◽

Posadas Herrera Guillermo ◽

Hiromi Hayashita-Kinoh ◽

Yasunobu Maruoka ◽

...

Keyword(s):

Stem Cells ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Dental Pulp ◽

Systemic Treatment ◽

Dental Pulp Stem Cells ◽

Mri Findings ◽

Systemic Injection ◽

Therapeutic Benefits

Abstract Background Duchenne muscular dystrophy (DMD) is an inherited progressive disorder that causes skeletal and cardiac muscle deterioration with chronic inflammation. Dental pulp stem cells (DPSCs) are attractive candidates for cell-based strategies for DMD because of their immunosuppressive properties. Therefore, we hypothesized that systemic treatment with DPSCs might show therapeutic benefits as an anti-inflammatory therapy. Methods To investigate the potential benefits of DPSC transplantation for DMD, we examined disease progression in a DMD animal model, mdx mice, by comparing them with different systemic treatment conditions. The DPSC-treated model, a canine X-linked muscular dystrophy model in Japan (CXMDJ), which has a severe phenotype similar to that of DMD patients, also underwent comprehensive analysis, including histopathological findings, muscle function, and locomotor activity. Results We demonstrated a therapeutic strategy for long-term functional recovery in DMD using repeated DPSC administration. DPSC-treated mdx mice and CXMDJ showed no serious adverse events. MRI findings and muscle histology suggested that DPSC treatment downregulated severe inflammation in DMD muscles and demonstrated a milder phenotype after DPSC treatment. DPSC-treated models showed increased recovery in grip-hand strength and improved tetanic force and home cage activity. Interestingly, maintenance of long-term running capability and stabilized cardiac function was also observed in 1-year-old DPSC-treated CXMDJ. Conclusions We developed a novel strategy for the safe and effective transplantation of DPSCs for DMD recovery, which included repeated systemic injection to regulate inflammation at a young age. This is the first report on the efficacy of a systemic DPSC treatment, from which we can propose that DPSCs may play an important role in delaying the DMD disease phenotype.

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Evaluating the potential of novel genetic approaches for the treatment of Duchenne muscular dystrophy

European Journal of Human Genetics ◽

10.1038/s41431-021-00811-2 ◽

2021 ◽

Author(s):

Vratko Himič ◽

Kay E. Davies

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Structural Integrity ◽

Viral Vector ◽

Exon Skipping ◽

Dystrophin Gene ◽

Pharmacological Treatments ◽

Genetic Sequencing ◽

Reading Frame ◽

Target Effects

AbstractDuchenne muscular dystrophy (DMD) is an X-linked progressive muscle-wasting disorder that is caused by a lack of functional dystrophin, a cytoplasmic protein necessary for the structural integrity of muscle. As variants in the dystrophin gene lead to a disruption of the reading frame, pharmacological treatments have only limited efficacy; there is currently no effective therapy and consequently, a significant unmet clinical need for DMD. Recently, novel genetic approaches have shown real promise in treating DMD, with advancements in the efficacy and tropism of exon skipping and surrogate gene therapy. CRISPR-Cas9 has the potential to be a ‘one-hit’ curative treatment in the coming decade. The current limitations of gene editing, such as off-target effects and immunogenicity, are in fact partly constraints of the delivery method itself, and thus research focus has shifted to improving the viral vector. In order to halt the loss of ambulation, early diagnosis and treatment will be pivotal. In an era where genetic sequencing is increasingly utilised in the clinic, genetic therapies will play a progressively central role in DMD therapy. This review delineates the relative merits of cutting-edge genetic approaches, as well as the challenges that still need to be overcome before they become clinically viable.

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Nutraceutical Screening in a Zebrafish Model of Muscular Dystrophy: Gingerol as a Possible Food Aid

Nutrients ◽

10.3390/nu13030998 ◽

2021 ◽

Vol 13 (3) ◽

pp. 998

Author(s):

Rosario Licitra ◽

Maria Marchese ◽

Letizia Brogi ◽

Baldassare Fronte ◽

Letizia Pitto ◽

...

Keyword(s):

Quality Of Life ◽

Muscular Dystrophy ◽

Genomic Medicine ◽

Neuromuscular Diseases ◽

Dystrophin Gene ◽

Neuromuscular Disorder ◽

Heme Oxygenase 1 ◽

Zebrafish Model ◽

Screening Study

Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is an inherited neuromuscular disorder that causes loss of muscle mass and motor skills. In the era of genomic medicine, there is still no known cure for DMD. In clinical practice, there is a growing awareness of the possible importance of nutrition in neuromuscular diseases. This is mostly the result of patients’ or caregivers’ empirical reports of how active substances derived from food have led to improved muscle strength and, thus, better quality of life. In this report, we investigate several nutraceutical principles in the sapje strain of zebrafish, a validated model of DMD, in order to identify possible natural products that, if supplemented in the diet, might improve the quality of life of DMD patients. Gingerol, a constituent of fresh ginger, statistically increased the locomotion of mutant larvae and upregulated the expression of heme oxygenase 1, a target gene for therapy aimed at improving dystrophic symptoms. Although three other compounds showed a partial positive effect on locomotor and muscle structure phenotypes, our nutraceutical screening study lent preliminary support to the efficacy and safety only of gingerol. Gingerol could easily be proposed as a dietary supplement in DMD.

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Oral bisphosphonate treatment in patients with Duchenne muscular dystrophy on long term glucocorticoid therapy

Neuromuscular Disorders ◽

10.1016/j.nmd.2020.06.005 ◽

2020 ◽

Vol 30 (7) ◽

pp. 599-610

Author(s):

Cuixia Tian ◽

Brenda L. Wong ◽

Lindsey Hornung ◽

Jane C. Khoury ◽

Irina Rybalsky ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Glucocorticoid Therapy ◽

Bisphosphonate Treatment ◽

Oral Bisphosphonate

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

JRSM Cardiovascular Disease ◽

10.1177/2048004019879581 ◽

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.

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