The Role of CRISPR/Cas9 in Revolutionizing Duchenne's Muscular Dystrophy Treatment: Opportunities and Obstacles DOI Creative Commons
Ali Ahsan,

Md. Rahman,

Danish Sheikh

et al.

Global Medical Genetics, Journal Year: 2024, Volume and Issue: 11(04), P. 349 - 357

Published: Oct. 18, 2024

Abstract Duchenne's muscular dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle degeneration, leading to loss of ambulation, respiratory failure, and premature death. It affects approximately 1 in 3,500 live male births caused mutations the dystrophin gene, which impairs fiber stability. Current treatments are limited managing symptoms slowing disease progression, with no curative therapies available. The advent CRISPR/Cas9 gene-editing technology has introduced promising approach for directly correcting genetic responsible DMD. This review explores potential as transformative therapy DMD, highlighting its successes preclinical models, challenges associated delivery, obstacles clinical application. While studies demonstrate efficacy restoring expression improving function, significant hurdles remain, including optimizing delivery methods ensuring long-term safety.

Language: Английский

Advanced Delivery Systems for Gene Editing: A Comprehensive Review from the GenE-HumDi COST Action Working group DOI Creative Commons
Alessia Cavazza, Francisco J Molina-Estévez, Álvaro Plaza Reyes

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(1), P. 102457 - 102457

Published: Jan. 18, 2025

Language: Английский

Citations

2
Transcriptional adaptation upregulates utrophin in Duchenne muscular dystrophy DOI Creative Commons

Lara Falcucci,

Christopher M. Dooley, Douglas Adamóski

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Abstract Duchenne muscular dystrophy (DMD) is a muscle-degenerating disease caused by mutations in the DMD gene, which encodes dystrophin protein 1,2 . Utrophin ( UTRN ), genetic and functional paralogue of , upregulated some patients 3–5 To further investigate this upregulation, we first developed an inducible messenger RNA (mRNA) degradation system for introducing premature termination codon (PTC) one its alternatively spliced exons. Inclusion PTC-containing exon triggers mutant mRNA decay upregulation. Notably, blocking nonsense-mediated results reversal whereas overexpressing does not. Furthermore, PTC minigenes wild-type cells causes as minigene containing self-cleaving ribozyme. place these findings therapeutic context, used splice-switching antisense oligonucleotides (ASOs) to induce skipping out-of-frame exons aiming introduce PTCs. We found that ASOs cause In addition, when using ASO restore reading frame myotubes derived from patient, actual treatment, upregulation was reduced. Altogether, indicate decay-based mechanism called transcriptional adaptation 6–8 plays key role patients, they highlight unexplored application ASOs, well ribozymes, inducing compensation via adaptation.

Language: Английский

Citations

2
Exploring new therapeutics for Duchenne muscular dystrophy and related cardiomyopathy DOI Open Access
Bin Li,

Weiyao Xiong,

Andrew Chia Hao Chang

et al.

Rare Disease and Orphan Drugs Journal, Journal Year: 2025, Volume and Issue: 5(2)

Published: March 26, 2025

Duchenne muscular dystrophy (DMD) is a severe and progressively debilitating X-linked recessive disorder caused by mutations in the DMD gene, which encodes dystrophin protein. This deficiency results progressive degeneration of both skeletal cardiac muscles. Currently, there no definitive cure for DMD, treatment primarily aims to slow disease progression manage symptoms. With widespread application respiratory support measures, cardiomyopathy has emerged as primary contributor morbidity mortality among patients at present. There an acute pressing need develop highly effective therapeutic strategies treating prevent onset heart failure. Various hypotheses have been proposed explain underlying mechanisms, including elevated levels inflammatory cytokines, dysregulated HDAC activity, disruptions ion balance, mitochondrial dysfunction, also considered potentially significant contributor. review article provide comprehensive overview various animal human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) models on cardiomyopathy. It provides summary current advancements ongoing efforts DMD-related cardiomyopathy, with focus innovative modalities, such mitochondria transplantation or targeting homeostasis. underscores dynamic evolving nature research dedicated developing treatments

Language: Английский

Citations

0
Advances in Duchenne Muscular Dystrophy: Diagnostic Techniques and Dystrophin Domain Insights DOI Open Access
Julija Sarvutiene, Arūnas Ramanavičius, Simonas Ramanavičius

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3579 - 3579

Published: April 10, 2025

Abnormalities in X chromosomes, either numerical or structural, cause X-linked disorders, such as Duchenne muscular dystrophy (DMD). Recent molecular and cytogenetic techniques can help identify DMD gene mutations. The accurate diagnosis of is crucial, directly impacting patient treatment management, genetics, the establishment effective prevention strategies. This review provides an overview chromosomal disorders affecting discusses how mutations Dystrophin domains impact detection accuracy. Firstly, efficiency use for genetic disease have, thus, become increasingly important. Secondly, artificial intelligence (AI) will be instrumental developing future therapies by enabling aggregation synthesis extensive heterogeneous datasets, thereby elucidating underlying mechanisms. However, despite advances diagnostic technology, understanding role remains a challenge. Therefore, this aims to synthesize complex information significantly advance it could affect care.

Language: Английский

Citations

0
Correction of exon 2, exon 2–9 and exons 8–9 duplications in DMD patient myogenic cells by a single CRISPR/Cas9 system DOI Creative Commons

Juliette Lemoine,

Auriane Dubois,

Alan R.L. Dorval

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 11, 2024

Language: Английский

Citations

1
The Role of CRISPR/Cas9 in Revolutionizing Duchenne's Muscular Dystrophy Treatment: Opportunities and Obstacles DOI Creative Commons
Ali Ahsan,

Md. Rahman,

Danish Sheikh

et al.

Global Medical Genetics, Journal Year: 2024, Volume and Issue: 11(04), P. 349 - 357

Published: Oct. 18, 2024

Abstract Duchenne's muscular dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle degeneration, leading to loss of ambulation, respiratory failure, and premature death. It affects approximately 1 in 3,500 live male births caused mutations the dystrophin gene, which impairs fiber stability. Current treatments are limited managing symptoms slowing disease progression, with no curative therapies available. The advent CRISPR/Cas9 gene-editing technology has introduced promising approach for directly correcting genetic responsible DMD. This review explores potential as transformative therapy DMD, highlighting its successes preclinical models, challenges associated delivery, obstacles clinical application. While studies demonstrate efficacy restoring expression improving function, significant hurdles remain, including optimizing delivery methods ensuring long-term safety.

Language: Английский

Citations

0