A Hypothesized Therapeutic Role of (Z)-Endoxifen in Duchenne Muscular Dystrophy (DMD).

What Can We Learn From Clinical Trials of Exon Skipping for DMD?

Genetic Complementation of Human Muscle Cells via Directed Stem Cell Fusion

Duchenne muscular dystrophy is a progressive X-linked recessive neuromuscular disorder resulting from pathogenic mutations in the DMD gene, which codes dystrophin. It is one of the essential structural proteins of muscle cells that maintains the integrity of cross-striated muscles. Duchenne muscular dystrophy causes progressive muscular weakness and, as a consequence, reduces life expectancy due to respiratory failure and/or heart failure. Glucocorticoids are considered the standard of care in Duchenne muscular dystrophy, although they are not highly effective and may lead to numerous adverse effects. For decades, many studies have been focused on finding an effective therapy for Duchenne muscular dystrophy; however, no etiology-oriented product is currently available for patients with Duchenne muscular dystrophy. That being said, the latest studies demonstrate that promising effective gene therapy for Duchenne muscular dystrophy is possible in the near future. The ongoing studies include approaches such as replacement therapy with shortened dystrophin forms and genome editing. Despite high efficacy of the approaches in vitro and in animal models, there is a number of challenges when it comes to treating human patients with Duchenne muscular dystrophy. The first challenge is the gene size — DMD is one of the largest genes, which makes it difficult to load it into viral vectors for delivery. Second, Duchenne muscular dystrophy is caused by over 7000 mutations, so creating universal gene therapies applicable to wide patient populations is problematic. Besides, low efficacy of genetic structure delivery and immune responses — both to the transgene and the viral vector — are a concern. Moreover, long-term sequelae of dystrophin deficiency could persist even if the protein expression is restored. The ongoing studies offer strategies to overcome the limitations above. This review aims to discuss the current challenges, the solutions to which may become a breakthrough in gene therapy for Duchenne muscular dystrophy and other hereditary diseases.

A manifesting female carrier of Duchenne muscular dystrophy: Importance of genetics for the dystrophinopathies.

Physiological Characterization of Muscle Strength With Variable Levels of Dystrophin Restoration in mdx Mice Following Local Antisense Therapy

Therapeutic potential of miRNAs in Duchenne muscular dystrophy and other neuromuscular diseases.

CRISPR/Cas9-Mediated Genome Editing Corrects Dystrophin Mutation in Skeletal Muscle Stem Cells in a Mouse Model of Muscle Dystrophy.

Gene therapy in the treatment of disease

Cardiology & Cardiac Surgery| May 01 2006 Steroid Treatment for Cardiac Function in Duchenne Muscular Dystrophy AAP Grand Rounds (2006) 15 (5): 58–59. https://doi.org/10.1542/gr.15-5-58-a Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Steroid Treatment for Cardiac Function in Duchenne Muscular Dystrophy. AAP Grand Rounds May 2006; 15 (5): 58–59. https://doi.org/10.1542/gr.15-5-58-a Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: cardiac function, duchenne's muscular dystrophy, steroid therapy Source: Markham LW, Spicer RL, Khoury PR, et al. Steroid therapy and cardiac function in Duchenne muscular dystrophy. Pediatr Cardiol. 2005;26:768–771. A 7-year experience at 2 institutions, Cincinnati’s Children’s Hospital Medical Center, Ohio, and the University of Iowa, Iowa City, was reviewed to test the hypothesis that corticosteroid treatment for long-term Duchenne muscular dystrophy (DMD)1,2 stabilizes cardiac muscle function. One hundred eleven subjects under age 21 years with DMD were divided into treated (steroid treatment >6 months, n=48) and untreated (steroid treatment <6 months, n=63) groups. Of the 48 treated patients, 29 received prednisone, and 19 received deflazacort (a derivative of prednisolone reported to cause less weight gain).3 Steroid treatment was begun at a mean age of 6.7 years and continued, on average, for 3 years. Treatment dose was not evaluated owing to variability within the study group. Ten subjects had had a prior course of corticosteroids (mean duration 4 years) that had been discontinued. Shortening fraction (SF), derived from M-mode echocardiography, was obtained in all cases and compared between the treated and untreated groups. The mean SF in the treated group was 36% compared with 30% in the untreated group (P<.001). For each year of age, the odds of a depressed SF increased 30% in the untreated group relative to the treated group. There were no demonstrable differences in cardiac function between the prednisone and deflazacort treatment subgroups. The group of patients who had a prior course of steroids maintained a mean SF of 35%, which was significantly higher than that of the untreated group but not demonstrably different from those actively receiving corticosteroids. The authors conclude that the clinical benefits of steroid therapy in DMD extend to cardiac function, that these benefits appear to persist even after discontinuation of therapy, and that the benefits outweigh the risks of side effects from chronic steroid use. Dr. Danford has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of a commercial product/device. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Pediatricians and cardiologists are taught as general dogma that chronic use of corticosteroids is to be avoided, in part because of the cardiovascular damage that might be done. Contrary to this widespread belief, the above report strongly suggests that in DMD these medications are actually helpful for the heart. The retrospective study design is a weakness that leaves room for other interpretations of the data. We wonder, of course, if the patients who received steroid treatment were the beneficiaries of more meticulous management of their disease apart from the use of steroids. The authors acknowledge the shortcomings of their retrospective study, but point out that the general noncardiac advantages of steroid treatment for DMD are so great that a placebo-controlled trial design, in which treatment is withheld from some subjects, would be unethical. The best evidence we have (and the best evidence we are likely to... You do not currently have access to this content.

Autologous Transplantation of SM/C-2.6+ Satellite Cells Transduced with Micro-dystrophin CS1 cDNA by Lentiviral Vector into mdx Mice

Gene Editing for Duchenne Muscular Dystrophy Using the CRISPR/Cas9 Technology: The Importance of Fine-tuning the Approach.

Transcription Factor Rational Design Improves Directed Differentiation of Human Mesenchymal Stem Cells Into Skeletal Myocytes

Efficacy of Multi-exon Skipping Treatment in Duchenne Muscular Dystrophy Dog Model Neonates

Efficient Whole-body Transduction with Trans-splicing Adeno-associated Viral Vectors

IL-6 Blockade as a Therapeutic Approach for Duchenne Muscular Dystrophy