Biological and genetic therapies for the treatment of Duchenne muscular dystrophy

Wilton-Clark, Harry; Yokota, Toshifumi

doi:10.1080/14712598.2022.2150543

Cited by 11 publications

(7 citation statements)

References 112 publications

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“…Since the first description of Duchenne muscular dystrophy in 1867 [ 94 ], various pharmacological efforts have failed to alter the natural course of the disease [ 95 , 96 ]. Recent updates of the pharmacological therapy for Duchenne muscular dystrophy are reported elsewhere [ 97 ].…”

Section: Pharmacological Therapymentioning

confidence: 99%

“…Ataluren (Translarna—PTC124) is a disease-modifying molecule for stop codon read-through therapy, which could help up to 10–15% of the DMD patients carrying nonsense mutations plus those carrying out of frame mutations [ 20 , 115 , 116 , 117 , 118 ]. However, there is no pharmacological drug that can compensate for the lack of dystrophin in muscle fibers [ 96 , 97 ].…”

Section: Pharmacological Therapymentioning

confidence: 99%

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Advances in Dystrophinopathy Diagnosis and Therapy

Saad,

Siciliano,

Angelini

2023

Biomolecules

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Dystrophinopathies are x-linked muscular disorders which emerge from mutations in the Dystrophin gene, including Duchenne and Becker muscular dystrophy, and dilated cardiomyopathy. However, Duchenne muscular dystrophy interconnects with bone loss and osteoporosis, which are exacerbated by glucocorticoids therapy. Procedures for diagnosing dystrophinopathies include creatine kinase assay, haplotype analysis, Southern blot analysis, immunological analysis, multiplex PCR, multiplex ligation-dependent probe amplification, Sanger DNA sequencing, and next generation DNA sequencing. Pharmacological therapy for dystrophinopathies comprises glucocorticoids (prednisone, prednisolone, and deflazacort), vamorolone, and ataluren. However, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and β-blockers are the first-line to prevent dilated cardiomyopathy in dystrophinopathy patients. Duchenne muscular dystrophy gene therapy strategies involve gene transfer, exon skipping, exon reframing, and CRISPR gene editing. Eteplirsen, an antisense-oligonucleotide drug for skipping exon 51 from the Dystrophin gene, is available on the market, which may help up to 14% of Duchenne muscular dystrophy patients. There are various FDA-approved exon skipping drugs including ExonDys-51 for exon 51, VyonDys-53 and Viltolarsen for exon 53 and AmonDys-45 for exon 45 skipping. Other antisense oligonucleotide drugs in the pipeline include casimersen for exon 45, suvodirsen for exon 51, and golodirsen for exon 53 skipping. Advances in the diagnosis and therapy of dystrophinopathies offer new perspectives for their early discovery and care.

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Section: Pharmacological Therapymentioning

confidence: 99%

Section: Pharmacological Therapymentioning

confidence: 99%

Advances in Dystrophinopathy Diagnosis and Therapy

Saad,

Siciliano,

Angelini

2023

Biomolecules

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“…Все препараты этой группы представляют цепочку антисмысловых нуклеотидов, которые специфически связываются с пре-мРНК, исключают соседний с делеционным участком экзон и восстанавливают открытую рамку считывания. В результате препарат-индуцированного пропуска экзона транслируется усеченный, но полностью функциональный белок дистрофин [23,25]. По результатам самого продолжительного, 4-летнего исследования препарата этой группы -вилтоларсена, у пациентов значительно повышается уровень дистрофин-положительных миофибрилл, улучшаются показатели функциональных тестов, что влияет на пролонгацию периода амбулаторности и качество жизни пациента.…”

Section: -3unclassified

Experience of observing patients with Duchenne myopathy

Minaycheva,

Petlina,

Ravzhaeva

et al. 2023

Rus. ž. det. nevrol.

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Duchenne muscular dystrophy is a genetically determined fatal disease with a steadily progressive course. It is characterized by the absence or sharp decrease (less than 3 % of the norm) of the dystrophin protein. In recent years, several drugs for pathogenetic treatment of Duchenne myodystrophy have appeared in Russia. Unfortunately, this therapy is not universal and can only be prescribed to patients with certain types and regions of mutations. Establishing an accurate diagnosis for patients will allow timely determination of observation tactics, effective implementation of preventive and rehabilitative measures, and obtaining pathogenetic treatment. Gene therapy is a perspective option. This article describes clinical cases of Duchenne myopathy in patients with different variants of mutations in the dystrophin gene against the background of pathogenetic therapy.

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“…Further, we are using our platform to investigate Duchenne muscular dystrophy (DMD) and identify potential therapeutic treatments (Bakooshli et al 2019 ; Ebrahimi et al 2021 ; Nguyen et al 2021 ). While there is considerable effort to develop gene-based (Zhang et al 2021 ) and cell-based therapies (Galli et al 2021 ) for DMD (Mollanoori et al 2021 ; Wilton-Clark and Yokota 2023 ), such treatments face a long developmental pipeline, and not all patients are eligible. While conventional therapeutic options remain limited (Kracht et al 2022 ), we believe that concomitant development of drug therapies that target root physiological perturbations has the potential to improve DMD symptoms and in the long run will complement other therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

Electron microscopic analysis of the influence of iPSC-derived motor neurons on bioengineered human skeletal muscle tissues

Nguyen,

Chávez-Madero,

Jacques

et al. 2024

Cell Tissue Res

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Abstract3D bioengineered skeletal muscle macrotissues are increasingly important for studies of cell biology and development of therapeutics. Tissues derived from immortalized cells obtained from patient samples, or from pluripotent stem cells, can be co-cultured with motor-neurons to create models of human neuromuscular junctions in culture. In this study, we present foundational work on 3D cultured muscle ultrastructure, with and without motor neurons, which is enabled by the development of a new co-culture platform. Our results show that tissues from Duchenne muscular dystrophy patients are poorly organized compared to tissues grown from healthy donor and that the presence of motor neurons invariably improves sarcomere organization. Electron micrographs show that in the presence of motor neurons, filament directionality, banding patterns, z-disc continuity, and the appearance of presumptive SSR and T-tubule profiles all improve in healthy, DMD-, and iPSC-derived muscle tissue. Further work to identify the underlying defects of DMD tissue disorganization and the mechanisms by which motor neurons support muscle are likely to yield potential new therapeutic approaches for treating patients suffering from Duchenne muscular dystrophy.

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Biological and genetic therapies for the treatment of Duchenne muscular dystrophy

Cited by 11 publications

References 112 publications

Advances in Dystrophinopathy Diagnosis and Therapy

Advances in Dystrophinopathy Diagnosis and Therapy

Experience of observing patients with Duchenne myopathy

Electron microscopic analysis of the influence of iPSC-derived motor neurons on bioengineered human skeletal muscle tissues

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