Gene editing and modulation for Duchenne muscular dystrophy

Stephenson, Anthony A.; Flanigan, Kevin M.

doi:10.1016/bs.pmbts.2021.01.029

Cited by 7 publications

(5 citation statements)

References 133 publications

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“…This therapeutic regimen maintains muscle strength and extends life expectancy, but corticosteroids long-term use could cause severe and very debilitating side effects (i.e., weight gain, glucose intolerance, hypertension, and depression) [ 41 , 42 ], thus making necessary the identification of an alternative and less toxic approach. Recently, the most intriguing therapeutical proposals are represented by stop-codon read-through therapy, gene replacement approaches, myoblast transfer therapy, and also drug-related inhibition of resident macrophages [ 43 , 44 , 45 ]. We suggest CB2 receptor agonism as an alternative, effective, and safe anti-inflammatory target for the therapy of DMD.…”

Section: Introductionmentioning

confidence: 99%

CB2 Receptor as Emerging Anti-Inflammatory Target in Duchenne Muscular Dystrophy

Argenziano

Pota

Paola

et al. 2023

IJMS

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Duchenne Muscular Dystrophy (DMD) is a very severe X-linked dystrophinopathy. It is due to a mutation in the DMD gene and causes muscular degeneration in conjunction with several secondary co-morbidities, such cardiomyopathy and respiratory failure. DMD is characterized by a chronic inflammatory state, and corticosteroids represent the main therapy for these patients. To contradict drug-related side effects, there is need for novel and more safe therapeutic strategies. Macrophages are immune cells stringently involved in both physiological and pathological inflammatory processes. They express the CB2 receptor, one of the main elements of the endocannabinoid system, and have been proposed as an anti-inflammatory target in several inflammatory and immune diseases. We observed a lower expression of the CB2 receptor in DMD-associated macrophages, hypothesizing its involvement in the pathogenesis of this pathology. Therefore, we analyzed the effect of JWH-133, a CB2 receptor selective agonist, on DMD-associated primary macrophages. Our study describes the beneficial effect of JWH-133 in counteracting inflammation by inhibiting pro-inflammatory cytokines release and by directing macrophages’ phenotype toward the M2 anti-inflammatory one.

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Section: Introductionmentioning

confidence: 99%

CB2 Receptor as Emerging Anti-Inflammatory Target in Duchenne Muscular Dystrophy

Argenziano

Pota

Paola

et al. 2023

IJMS

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“… 30 , 31 We also note that PPMO approaches are likely to be safer than somatic gene editing approaches, which carry risk of significant off-target effects. 32 …”

Section: Discussionmentioning

confidence: 99%

Systemic PPMO-mediated dystrophin expression in the Dup2 mouse model of Duchenne muscular dystrophy

Gushchina¹,

Vetter²,

Frair³

et al. 2022

Molecular Therapy - Nucleic Acids

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“…Over the past decade, gene editing has moved to the forefront with the identification of mechanisms of DNA repair ( Stephenson and Flanigan, 2021 ). The CRISPR-Cas system has made it possible for research labs all around the world to successfully incorporate gene editing into their work ( Jinek et al, 2012 ; Mali et al, 2013 ; Perez-Pinera et al, 2013 ).…”

Section: Therapeutic Strategies For Dmdmentioning

confidence: 99%

Duchenne muscular dystrophy: disease mechanism and therapeutic strategies

et al. 2023

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Duchenne muscular dystrophy (DMD) is a severe, progressive, and ultimately fatal disease of skeletal muscle wasting, respiratory insufficiency, and cardiomyopathy. The identification of the dystrophin gene as central to DMD pathogenesis has led to the understanding of the muscle membrane and the proteins involved in membrane stability as the focal point of the disease. The lessons learned from decades of research in human genetics, biochemistry, and physiology have culminated in establishing the myriad functionalities of dystrophin in striated muscle biology. Here, we review the pathophysiological basis of DMD and discuss recent progress toward the development of therapeutic strategies for DMD that are currently close to or are in human clinical trials. The first section of the review focuses on DMD and the mechanisms contributing to membrane instability, inflammation, and fibrosis. The second section discusses therapeutic strategies currently used to treat DMD. This includes a focus on outlining the strengths and limitations of approaches directed at correcting the genetic defect through dystrophin gene replacement, modification, repair, and/or a range of dystrophin-independent approaches. The final section highlights the different therapeutic strategies for DMD currently in clinical trials.

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Gene editing and modulation for Duchenne muscular dystrophy

Cited by 7 publications

References 133 publications

CB2 Receptor as Emerging Anti-Inflammatory Target in Duchenne Muscular Dystrophy

CB2 Receptor as Emerging Anti-Inflammatory Target in Duchenne Muscular Dystrophy

Systemic PPMO-mediated dystrophin expression in the Dup2 mouse model of Duchenne muscular dystrophy

Duchenne muscular dystrophy: disease mechanism and therapeutic strategies

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