Taking ACTION to detect myocarditis related to recombinant gene transfer therapy for Duchenne Muscular Dystrophy; Consensus recommendations for cardiac surveillance DOI Creative Commons
Beth D. Kaufman, Aravindhan Veerapandiyan, Jonathan H. Soslow

et al.

Journal of Neuromuscular Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

A viral vector recombinant gene transfer therapy (GTT) has recently been approved by the FDA for males of all ages with Duchenne Muscular Dystrophy (DMD) without limitations regarding preexisting cardiac impairment. Acute myocarditis is a potential life-threatening short-term complication that reported following GTT. This immune mediated response can range from troponin elevation to rapid cardiovascular compromise and death, particularly in those abnormal status at baseline. Early detection essential optimize outcomes. The primary objective this consensus statement advocate caution DMD GTT patient selection initiate preemptive monitoring who may be increased risk adverse events. Secondary deepen our understanding short long-term impact therapies on heart. national learning network pediatric cardiologists expertise developed recommendations surveillance receiving based available evidence expert opinion. treatment plan standard high patients was developed. Partnership prescribers identify patient-specific considerations might influence events alter post infusion management plans. Consistency practices across centers will expedite knowledge short- effects DMD.

Language: Английский

The latest developments in synthetic approaches to duchenne muscular dystrophy DOI

Lucy M. Johnson,

Tariq G. Pulskamp,

Daniel J. Berlau

et al.

Expert Review of Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Duchenne muscular dystrophy (DMD) is a rare X-linked genetic disorder caused by mutations in the dystrophin gene, leading to an almost complete absence of dystrophin, which essential for muscle cell structure and function. This resulting deterioration fibrosis, eventually causes respiratory failure cardiomyopathy. While there currently no cure, existing therapies aim prolong survival alleviate symptoms. paper reviews current emerging DMD, focusing on their safety efficacy. Although corticosteroids remain standard treatment, newly approved drugs such as exon-skipping therapies, vamorolone, delandistrogene moxeparvovec, givinostat provide new treatment options. Additionally, future including gene therapy, stem treatments, anti-fibrotic agents, show promise clinical application. Advancements DMD treatments have expanded patient therapy offers potential correcting defect alleviating symptoms, most cost-effective well-researched treatment. partly due lack compelling long-term efficacy data therapies. The accelerated FDA review process has enabled faster approval medications; however many provided minimal benefit patients. Despite these challenges, continued drug development innovative research offer hope

Language: Английский

Citations

0
Delandistrogene Moxeparvovec Gene Therapy in Individuals With Duchenne Muscular Dystrophy: Evidence in Focus DOI
Maryam Oskoui,

Tracie A. Caller,

Julie Parsons

et al.

Neurology, Journal Year: 2025, Volume and Issue: 104(11)

Published: May 14, 2025

This Evidence in Focus reviews the current evidence on efficacy and adverse effects of delandistrogene moxeparvovec patients with Duchenne muscular dystrophy (DMD) presents clinical considerations regarding use. The author panel systematically reviewed available trial data DMD. risk bias was evaluated using American Academy Neurology's 2017 therapeutic classification scheme. Safety information, regulatory decisions, context were also reviewed. Six trials identified, which 4 had peer-reviewed available. From studies (2 Class I 2 III), exposure are 134 boys, 128 ambulatory aged ≥4 to <8 years. Both failed meet primary functional motor outcome as assessed by change North Star Ambulatory Assessment score. Several secondary outcomes demonstrated improvement treatment group small effect sizes, not meeting statistical significance from hierarchical analysis. Corticosteroid dose higher first 12 weeks after infusion, potentially contributing measured differences between groups. similar across multiple treatment-related events, including peri-infusion effects, immune myositis myocarditis, thrombocytopenia, liver toxicity. One death has been reported an individual who treated outside a trial. Despite demonstrating its outcome, approved US Food Drug Administration (FDA) for use boys decision supported relative safety product measures phase 3 As drug may now be actively prescribed United States other countries FDA approval, providers should aware limitations need monitor immune-related side injury, require expanded infrastructure. Additional careful collection real-world will essential establish short-term long-term effectiveness inform understanding benefits risks lifespan.

Language: Английский

Citations

0
Therapeutic Application and Structural Features of Adeno-Associated Virus Vector DOI Creative Commons

Yasunari Matsuzaka,

Ryu Yashiro

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(8), P. 8464 - 8498

Published: Aug. 2, 2024

Adeno-associated virus (AAV) is characterized by non-pathogenicity, long-term infection, and broad tropism actively developed as a vector for gene therapy products. AAV classified into more than 100 serotypes based on differences in the amino acid sequence of capsid protein. Endocytosis involves uptake viral particles accessory receptors during infection. After entry cell, they are transported to nucleus through nuclear pore complex. AAVs mainly use proteoglycans enter cells, but types sugar chains that have binding ability different. Therefore, it necessary properly evaluate primary structure receptor proteins, such sequences post-translational modifications, including glycosylation, higher-order folding entire three-dimensional (3D) functional domains, ensure efficacy safety biopharmaceuticals. To further enhance safety, improve efficiency transfer target reduce amount administered, prevent infection non-target cells.

Language: Английский

Citations

3
Systemic Treatment of Body‐Wide Duchenne Muscular Dystrophy Symptoms DOI Creative Commons
Patryk Konieczny

Clinical Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 116(6), P. 1472 - 1484

Published: July 4, 2024

Duchenne muscular dystrophy (DMD) is a fatal X‐linked disease that leads to premature death due the loss of dystrophin. Current strategies predominantly focus on therapeutic treatment affected skeletal muscle tissue. However, certain results point fact with successful muscle, DMD‐exposed latent phenotypes in tissues, such as cardiac and smooth might lead adverse effects even death. Likewise, it now clear absence dystrophin affects function nervous system, this phenotype more pronounced when shorter dystrophins are absent, addition full‐length present muscle. Here, I systemic aspects DMD, highlighting ubiquitous expression gene human tissues. Furthermore, describe have been tested clinic unresolved questions regarding distinct isoforms, possibility current tackle relate their absence.

Language: Английский

Citations

1
Equitable Access of Delandistrogene Moxeparvovec for Duchenne Muscular Dystrophy Patients: A Call for Discussion DOI

Omer Abdul Hamid,

D. Micah Hester, Susan Matesanz

et al.

Pediatric Neurology, Journal Year: 2024, Volume and Issue: 159, P. 33 - 34

Published: July 30, 2024

Language: Английский

Citations

1
Mechanisms of Chimeric Cell Therapy in Duchenne Muscular Dystrophy DOI Creative Commons
Maria Siemionow,

Anna Ziemiecka,

Katarzyna Bożyk

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 1996 - 1996

Published: Sept. 2, 2024

Despite scientific efforts, there is no cure for Duchenne muscular dystrophy (DMD), a lethal, progressive, X-linked genetic disorder caused by mutations in the dystrophin gene. DMD leads to cardiac and skeletal muscle weakness, resulting premature death due cardio-pulmonary complications. We have developed Dystrophin Expressing Chimeric (DEC) cell therapy, DT-DEC01, fusing human myoblasts from healthy donors patients. Preclinical studies on DEC cells showed increased expression improved cardiac, pulmonary, function after intraosseous administration. Our clinical study confirmed safety efficacy of DT-DEC01 therapy up 24 months post-administration. In this study, we conducted vitro assays test composition potency assessing chimerism level presence dystrophin, desmin, myosin heavy chain. Myoblast fusion resulted transfer donor mitochondria creation chimeric within DT-DEC01. The Pappenheim assay myotube formation final product. This highlights unique properties their relevance treatment mechanisms.

Language: Английский

Citations

0
Acute Liver Injury Following Delandistrogene Moxeparvovec Gene Therapy Requiring Intravenous Immunoglobulin DOI
Ruthwik Duvuru, Silke Neumann,

Eniya Beemarajan

et al.

Pediatric Neurology, Journal Year: 2024, Volume and Issue: 163, P. 1 - 3

Published: Nov. 14, 2024

Language: Английский

Citations

0
Taking ACTION to detect myocarditis related to recombinant gene transfer therapy for Duchenne Muscular Dystrophy; Consensus recommendations for cardiac surveillance DOI Creative Commons
Beth D. Kaufman, Aravindhan Veerapandiyan, Jonathan H. Soslow

et al.

Journal of Neuromuscular Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

A viral vector recombinant gene transfer therapy (GTT) has recently been approved by the FDA for males of all ages with Duchenne Muscular Dystrophy (DMD) without limitations regarding preexisting cardiac impairment. Acute myocarditis is a potential life-threatening short-term complication that reported following GTT. This immune mediated response can range from troponin elevation to rapid cardiovascular compromise and death, particularly in those abnormal status at baseline. Early detection essential optimize outcomes. The primary objective this consensus statement advocate caution DMD GTT patient selection initiate preemptive monitoring who may be increased risk adverse events. Secondary deepen our understanding short long-term impact therapies on heart. national learning network pediatric cardiologists expertise developed recommendations surveillance receiving based available evidence expert opinion. treatment plan standard high patients was developed. Partnership prescribers identify patient-specific considerations might influence events alter post infusion management plans. Consistency practices across centers will expedite knowledge short- effects DMD.

Language: Английский

Citations

0