Clicky

Conditional Dystrophin ablation causes profound effects on muscle development, neurobehavior, and extracellular matrix pathways

15 April 25 Articles ، DystroBlog | Neuromuscular Disease Research & News ، Matthew S Alexander ، Louis M. Kunkel ، Karyn Esser conditional dystrophin knockout mouse model ، dystrophin ablation in skeletal muscle ، Purkinje neuron-specific dystrophin deletion ، dystrophin and neurobehavioral deficits ، extracellular matrix dysregulation in DMD ، Duchenne muscular dystrophy gene therapy mouse model ، RNA-seq analysis in dystrophin-deficient muscle ، muscle regeneration after dystrophin loss ، Dp427m isoform function in muscle stem cells ، Cre-lox dystrophin deletion strategy ، muscle-specific dystrophin loss and fibrosis ، Dmd exon 52 conditional knockout in mice ، behavior changes in brain-specific Dmd KO mice ، ECM and cytokine gene expression in dystrophic muscle ، mild phenotype of postnatal dystrophin ablation
Conditional Dystrophin ablation causes profound effects on muscle development, neurobehavior, and extracellular matrix pathways
This study shows that deleting dystrophin specifically in muscle stem cells leads to major changes in muscle growth and behavior. It highlights a possible muscle-brain signaling axis with broad implications for DMD therapy.
more

Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery

22 March 25 Articles ، Douglas Millay ، Christopher W Ward ، Jeffrey Chamberlain targeted gene therapy for Duchenne muscular dystrophy treatment ، engineered viruses delivering genes specifically to muscle tissue ، selective muscle cell targeting using Myomaker and Myomerger proteins ، pseudotyped lentiviral vectors for skeletal muscle gene therapy ، re-dosable viral vectors for safe and sustained gene expression ، fusion-protein-based gene delivery to regenerating muscle fibers ، immune-safe strategies for repeated muscle gene therapy injections ، muscle-specific gene therapy with minimized off-target effects ، restoring dystrophin expression in DMD using μDys gene delivery ، novel viral platforms for efficient and precise gene delivery to muscle
Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery
This study introduces muscle-specific pseudotyped viruses using natural fusion proteins (Myomaker & Myomerger) to deliver gene therapy directly and selectively to muscle tissue—offering new hope for muscular diseases like DMD.
more

Recent developments and industry interest in gene therapy for duchenne muscular dystrophy

13 March 25 Articles ، Toshifumi Yokota Gene therapy for Duchenne muscular dystrophy ، CRISPR-based gene editing techniques ، micro-dystrophin therapy ، AAV vector-based treatment ، gene therapy safety challenges ، FDA approvals for gene therapy
Recent developments and industry interest in gene therapy for duchenne muscular dystrophy
Recent Developments and Industry Interest in Gene Therapy for Duchenne Muscular Dystrophy Introduction Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that causes progressive muscle degeneration. This condition is caused by mutations in the DMD gene, which encodes a crucial protein for muscle stability. Symptoms usually appear between ages 2 and 5, leading to muscle weakness and, eventually, respiratory or cardiac failure. While antisense oligonucleotides have been approved to …
more

Antisense Oligonucleotides Conjugated with Lipophilic Compounds: Synthesis and In Vitro Evaluation of Exon Skipping in Duchenne Muscular Dystrophy

06 March 25 Articles Duchenne Muscular Dystrophy ، Exon skipping ، Duchenne muscular dystrophy ، antisense oligonucleotides ، exon skipping ، lipophilic conjugation ، ursodeoxycholic acid
Antisense Oligonucleotides Conjugated with Lipophilic Compounds: Synthesis and In Vitro Evaluation of Exon Skipping in Duchenne Muscular Dystrophy
This study examines how lipophilic-modified antisense oligonucleotides (ASOs) enhance exon skipping in Duchenne muscular dystrophy (DMD). The results show improved cellular uptake, nanoparticle formation, and higher exon-skipping efficiency, making these ASOs promising therapeutic candidates.
more

In Silico Screening Based on Predictive Algorithms as a Design Tool for Exon Skipping Oligonucleotides in Duchenne Muscular Dystrophy

06 March 25 Articles ، Toshifumi Yokota ، Yusuke Echigoya ، Vincent Mouly ، Luis Garcia Duchenne Muscular Dystrophy ، Exon skipping ، Duchenne muscular dystrophy ، antisense oligonucleotides ، computational modeling ، efficacy prediction
In Silico Screening Based on Predictive Algorithms as a Design Tool for Exon Skipping Oligonucleotides in Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a genetic disorder leading to muscle degeneration. This study introduces a predictive computational model for exon skipping therapy, achieving 89% accuracy for PMOs and 76% accuracy for 2’-O-Methyl RNA, aiding in oligonucleotide selection.
more

Systemic delivery of an AAV9 exonskipping vector significantly improves or prevents features of Duchenne muscular dystrophy in the Dup2 mouse

05 January 25 Articles ، Kevin Flanigan ، Robert Weiss Duchenne muscular dystrophy gene therapy ، Dystrophin restoration in DMD ، AAV9 exon skipping therapy for DMD ، scAAV9-U7snRNA for exon 2 skipping ، Dup2 mouse model of DMD ، Neonatal gene therapy for DMD ، Long-term exon skipping efficiency ، Prednisolone co-treatment in DMD
Systemic delivery of an AAV9 exonskipping vector significantly improves or prevents features of Duchenne muscular dystrophy in the Dup2 mouse
This study evaluates AAV9-U7 exon skipping therapy in the Dup2 mouse model of Duchenne muscular dystrophy (DMD). A single injection in adults restored up to 95% exon skipping, improving muscle structure and function. Neonatal treatment achieved 99% dystrophin-positive fibers and near-complete disease correction over six months. Findings suggest AAV9-based exon skipping provides long-lasting dystrophin restoration, supporting its potential as a clinical therapy for DMD exon 2 duplications.
more

Increase in Full-Length Dystrophin by Exon Skipping in Duchenne Muscular Dystrophy Patients with Single Exon Duplications: An Open-label Study

02 January 25 Articles ، Linda Pax Lowes ، Kevin Flanigan Duchenne muscular dystrophy exon skipping ، Dystrophin restoration in DMD ، Single exon duplication in DMD ، Casimersen and golodirsen therapy ، Exon 45 and exon 53 skipping therapy ، Open-label exon skipping study ، Antisense oligonucleotides for DMD ، Gene therapy for rare DMD mutations
Increase in Full-Length Dystrophin by Exon Skipping in Duchenne Muscular Dystrophy Patients with Single Exon Duplications: An Open-label Study
This open-label study evaluates casimersen and golodirsen in DMD patients with rare single exon duplications (exon 45 or 53). Over 48 weeks, dystrophin levels increased from 0.94% to 5.1%, with dystrophin-positive fibers rising from 14% to 50%. RT-PCR confirmed exon skipping, while pulmonary and cardiac functions remained stable. No major safety concerns emerged, but longer trials with larger cohorts are needed to assess long-term clinical benefits. These findings highlight exon skipping as a targeted therapy for rare DMD mutations.
more

Challenges of Assessing Exon 53 Skipping of the HumanDMD Transcript with Locked Nucleic Acid-ModifiedAntisense Oligonucleotides in a Mouse Modelfor Duchenne Muscular Dystrophy

02 January 25 Articles ، Annemieke Aartsma-Rus ، Anastasia Khvorova ، Masad J. Damha Duchenne muscular dystrophy exon 53 skipping ، Locked nucleic acid (LNA) AONs for DMD ، Antisense oligonucleotide therapy DMD ، RNA analysis challenges in exon skipping ، LNA-FRNA and LNA-2′OMe modifications ، hDMDdel52/mdx mouse model for DMD ، Exon skipping efficiency vs. dystrophin restoration ، AON design optimization for DMD treatment
Challenges of Assessing Exon 53 Skipping of the HumanDMD Transcript with Locked Nucleic Acid-ModifiedAntisense Oligonucleotides in a Mouse Modelfor Duchenne Muscular Dystrophy
This study assesses exon 53 skipping in Duchenne muscular dystrophy (DMD) using locked nucleic acid (LNA)-modified antisense oligonucleotides (AONs) in a humanized DMD mouse model. While certain LNA-AONs (LNA-FRNA, LNA-2′OMe) achieved high exon skipping, actual dystrophin restoration was minimal due to RNA interference issues affecting cDNA synthesis. Optimizing AON designs, RNA analysis methods, and alternative exon targets is crucial for improving therapeutic efficacy in DMD exon skipping therapies.
more

Next Generation Exon 51 Skipping Antisense Oligonucleotides for Duchenne Muscular Dystrophy

28 December 24 Articles ، Annemieke Aartsma-Rus ، Judith van Deutekom Next-generation exon skipping AONs ، Duchenne muscular dystrophy exon 51 therapy ، Advanced antisense oligonucleotides for DMD ، Locked nucleic acids (LNAs) in exon skipping ، Becker muscular dystrophy dystrophin restoration ، Novel exon 51 AON chemical modifications ، Preclinical DMD exon skipping studies ، Capillary Western immunoassay dystrophin levels
Next Generation Exon 51 Skipping Antisense Oligonucleotides for Duchenne Muscular Dystrophy
This study advances next-generation exon 51 skipping antisense oligonucleotides (AONs) for Duchenne muscular dystrophy (DMD) by incorporating novel chemical modifications like 5-methylcytosine and locked nucleic acids (LNAs). Screening 100+ AONs identified an optimized target site, achieving 65-fold higher exon skipping and restoring 30-40% dystrophin levels in preclinical models. These AONs demonstrated improved muscle integrity, enhanced motor function, and a favorable safety profile, marking a major step toward safer, more effective DMD therapies.
more

A mini review and implementation model for using ataluren to treat nonsense mutation Duchenne muscular dystrophy

21 December 24 Articles ، Erik Landfeldt ، Már Tulinius ، Thomas Sejersen Ataluren treatment for nmDMD ، Nonsense mutation Duchenne muscular dystrophy ، Ataluren clinical guidelines ، DMD stop codon read-through therapy ، Implementation model for ataluren in Sweden ، Pulmonary function in nmDMD patients ، Economic challenges of ataluren therapy ، Multidisciplinary care for DMD
A mini review and implementation model for using ataluren to treat nonsense mutation Duchenne muscular dystrophy
This mini-review explores ataluren therapy for nonsense mutation Duchenne muscular dystrophy (nmDMD), covering clinical guidelines and an implementation model for Sweden. Ataluren delays muscle degeneration, preserves ambulation, and improves pulmonary function in ambulatory nmDMD patients. A proposed centralized expert committee would oversee access and monitoring. Despite high costs, equitable treatment strategies aim to enhance care and outcomes for DMD patients with nonsense mutations.
more

Identification of the Wnt signal peptide that directs secretion on extracellular vesicles

14 December 24 Articles ، Michael A. Rudnicki ، Ehsan Javandoost ، Rashmi Kothary Wnt7a extracellular vesicle secretion ، Exosome-Binding Peptide (EBP) function ، Wnt signaling and muscle regeneration ، Coatomer proteins in EV secretion ، Duchenne muscular dystrophy Wnt7a therapy ، Long-range Wnt protein signaling ، EV-based drug delivery systems ، Noncanonical protein secretion pathways
Identification of the Wnt signal peptide that directs secretion on extracellular vesicles
This study identifies Exosome-Binding Peptide (EBP) as a key Wnt7a secretion signal for extracellular vesicles (EVs), enabling long-range intercellular signaling. EBP binds to coatomer proteins (COPA & COPB2), anchoring Wnt7a to EVs and enhancing muscle repair. This mechanism, conserved in Wnt proteins, has implications for neuromuscular disease therapies, including Duchenne muscular dystrophy (DMD). EBP-guided EV delivery could revolutionize targeted drug and protein therapies, bypassing traditional systemic delivery challenges.
more

Exon skipping for Duchenne muscular dystrophy: a systematic review and metaanalysis

08 December 24 Articles ، En Kimura ، Yuko Shimizu-Motohashi Duchenne muscular dystrophy exon skipping ، Systematic review exon-skipping therapy ، Meta-analysis of DMD treatments ، Eteplirsen vs. drisapersen efficacy ، 6-minute walk test (6MWT) in DMD ، North Star Ambulatory Assessment (NSAA) in exon skipping ، Adverse effects of exon-skipping drugs ، Future of exon-skipping therapies
Exon skipping for Duchenne muscular dystrophy: a systematic review and metaanalysis
This systematic review and meta-analysis evaluated five randomized controlled trials (RCTs) on exon-skipping therapies for Duchenne muscular dystrophy (DMD). Analyzing 322 patients, the study assessed eteplirsen and drisapersen using 6MWT and NSAA scores. Results showed no significant improvement over placebo. Drisapersen (6 mg/kg) provided minor benefits but had renal toxicity risks, while eteplirsen showed fewer side effects but lacked robust efficacy data. The study calls for long-term trials to confirm exon skipping’s clinical impact.
more

Exon-Skipping in Duchenne Muscular Dystrophy

05 December 24 Articles ، Eric P. Hoffman ، Paula R. Clemens ، Shin’ichi Takeda Micro-dystrophin gene therapy ، Duchenne muscular dystrophy exon skipping ، Antisense oligonucleotides (AONs) for DMD ، Eteplirsen and viltolarsen therapy ، Becker muscular dystrophy phenotype conversion ، Dystrophin restoration therapies ، Stop codon read-through drugs for DMD ، Future treatments for muscular dystrophy
Exon-Skipping in Duchenne Muscular Dystrophy
Exon-skipping therapy aims to restore dystrophin production in Duchenne muscular dystrophy (DMD) by using antisense oligonucleotides (AONs) to bypass mutations. Eteplirsen and viltolarsen target exon 51, producing a truncated but functional dystrophin protein. While promising, challenges remain, including low dystrophin levels and variable patient responses. Gene therapy and stop codon read-through drugs offer alternative strategies. Early intervention and combination therapies may improve outcomes for DMD patients.
more

Exon skipping and dystrophin restoration in patientswith Duchenne muscular dystrophy after systemicphosphorodiamidate morpholino oligomer treatment:an open-label, phase 2, dose-escalation study

17 November 24 Articles ، Volker Straub ، Ryszard Kole ، Steve Wilton ، George Dickson ، Karen Anthony ، Francesco Muntoni ، Virginia Arechavala-Gomeza ، Kate Bushby ، Jennifer Morgan Duchenne muscular dystrophy exon skipping ، Dystrophin restoration in DMD ، AVI-4658 phosphorodiamidate morpholino oligomer ، DMD clinical trial phase 2 ، Exon 51 skipping therapy ، PMO treatment for muscular dystrophy ، AVI BioPharma DMD study ، Dose-escalation exon skipping trial
Exon skipping and dystrophin restoration in patientswith Duchenne muscular dystrophy after systemicphosphorodiamidate morpholino oligomer treatment:an open-label, phase 2, dose-escalation study
This phase 2, open-label trial evaluated AVI-4658 (PMO) therapy in 19 boys with Duchenne muscular dystrophy (DMD), assessing exon 51 skipping and dystrophin restoration. The drug was well tolerated, showing dose-dependent dystrophin expression, with significant improvements at higher doses. Increased dystrophin correlated with protein localization and reduced inflammation, though responses varied. Findings support AVI-4658 as a potential disease-modifying treatment, emphasizing the need for long-term trials to confirm clinical benefits.
more

Dystrophin Restoration after Adeno-Associated Virus U7eMediated Dmd Exon Skipping Is Modulated by Muscular Exercise in the Severe D2-Mdx Duchenne Muscular Dystrophy Murine Model

17 November 24 Articles ، Capucine Trollet ، Arnaud Ferry Duchenne muscular dystrophy gene therapy ، Dystrophin restoration in DMD ، AAV-U7 exon skipping for DMD ، Exercise and gene therapy in DMD ، D2-mdx mouse model for DMD ، Muscle regeneration in dystrophy ، Voluntary exercise and dystrophin levels ، DMD treatment strategies
Dystrophin Restoration after Adeno-Associated Virus U7eMediated Dmd Exon Skipping Is Modulated by Muscular Exercise in the Severe D2-Mdx Duchenne Muscular Dystrophy Murine Model
This study investigates how voluntary exercise impacts AAV-U7-mediated exon skipping therapy in D2-mdx mice with Duchenne muscular dystrophy (DMD). Exercise did not worsen muscle damage or reduce viral genome expression, though dystrophin-positive muscle area declined from 80% to 65%. Despite this, gene therapy remained effective, and muscle strength improved. Findings suggest exercise can be integrated into DMD treatments without major therapy disruption, though long-term effects need further study.
more

Recent Posts

Categories

I'd be delighted if you could explore the other sections of my website.

Biochemist Researcher . YouTuber . Medical Laboratory Tech

!I am Ali Nik Akhtar

Personal Website​​​​​​​

If you have any questions or would like to discuss further, please feel free to email me. I would be delighted to get to know you better.

Ready to start a collaboration...​​​​​​​

Contact Me

Nikakhtar422@gmail.com

All rights reserved. This website belongs to Ali Nik Akhtar.