Perspectives on the advances in the pharmacotherapeutic management of Duchenne muscular dystrophy

Kracht, Kelsie D; Eichorn, Nicole L; Berlau, Daniel J.

doi:10.1080/14656566.2022.2130246

Cited by 4 publications

(2 citation statements)

References 71 publications

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“…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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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

View full text Add to dashboard Cite

show abstract

“…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 & 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 have 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. 2023

Preprint

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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 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 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 trophic 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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Pharmacological Treatments and Therapeutic Targets in Muscle Dystrophies Generated by Alterations in Dystrophin-Associated Proteins

Luna-Angulo,

Landa-Solís,

Escobar-Cedillo

et al. 2024

Medicina

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Muscular dystrophies (MDs) are a heterogeneous group of diseases of genetic origin characterized by progressive skeletal muscle degeneration and weakness. There are several types of MDs, varying in terms of age of onset, severity, and pattern of the affected muscles. However, all of them worsen over time, and many patients will eventually lose their ability to walk. In addition to skeletal muscle effects, patients with MDs may present cardiac and respiratory disorders, generating complications that could lead to death. Interdisciplinary management is required to improve the surveillance and quality of life of patients with an MD. At present, pharmacological therapy is only available for Duchene muscular dystrophy (DMD)—the most common type of MD—and is mainly based on the use of corticosteroids. Other MDs caused by alterations in dystrophin-associated proteins (DAPs) are less frequent but represent an important group within these diseases. Pharmacological alternatives with clinical potential in patients with MDs and other proteins associated with dystrophin have been scarcely explored. This review focuses on drugs and molecules that have shown beneficial effects, mainly in experimental models involving alterations in DAPs. The mechanisms associated with the effects leading to promising results regarding the recovery or maintenance of muscle strength and reduction in fibrosis in the less-common MDs (i.e., with respect to DMD) are explored, and other therapeutic targets that could contribute to maintaining the homeostasis of muscle fibers, involving different pathways, such as calcium regulation, hypertrophy, and maintenance of satellite cell function, are also examined. It is possible that some of the drugs explored here could be used to affordably improve the muscular function of patients until a definitive treatment for MDs is developed.

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Perspectives on the advances in the pharmacotherapeutic management of Duchenne muscular dystrophy

Cited by 4 publications

References 71 publications

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

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

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

Pharmacological Treatments and Therapeutic Targets in Muscle Dystrophies Generated by Alterations in Dystrophin-Associated Proteins

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