MyoDys45-55 / MyoGene Bio - LARVOL DELTA

Transcytotic transportation of size-controlled nanocarriers into dystrophic skeletal muscle leads to therapeutic outcome in mice. (PubMed, Nat Commun) - "Further, we encapsulate tamoxifen, a repurposed drug, into optimized MSNPs. This intervention increases utrophin expression, reduces fibrosis, and diminishes myofiber necrosis, resulting in improved muscle health and strength. Our results establish size-tuned, transcytosis-enabled nanocarriers as a transformative strategy for targeted drug delivery to dystrophic muscle, paving the way for nanomedicine-based therapies in DMD and potentially other muscle disorders."

Journal • Preclinical • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Muscular Dystrophy

Identifying Muscle Stem Cell Tropic AAV Variants Through Directed Evolution (ASGCT 2025) - "While further characterization must be done, these new variants provide a potential new platform for achieving long-term dystrophin restoration and durability when AAV is used to deliver CRISPR components in DMD and other myogenic diseases that involve muscle degeneration and regeneration. Disease Focus of Abstract:Muscular Dystrophy (all forms)"

Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients. (PubMed, Mol Ther Methods Clin Dev) - "Three of these expanded clumps could be assigned to prior human herpesvirus infections, two of which were present in the participant that exhibited TMA. These data provide insight on the mechanistic basis of human immune-AAV interactions and lay a foundation for improved understanding of why TMA arises in some patients and not others."

Gene therapy • Immune cell • Journal • CNS Disorders • Duchenne Muscular Dystrophy • Epstein-Barr Virus Infections • Gene Therapies • Genetic Disorders • Infectious Disease • Muscular Dystrophy

Single-Cell and TCR Analysis from Duchenne Muscular Dystrophy Patients Treated with AAV9 Mini-Dystrophin Reveals an Expansion of Human Herpesvirus-Specific T-Cells in a Patient That Exhibited Thrombotic Microangiopathy (ASGCT 2024) - "We found similar TCRs in two patients that only appeared after treatment, and unexpectedly, a separate patient where T-cells with TCRs reactive to human-herpesviruses increased after treatment. TCRs could be used in future to track immune responses in AAV-treated patients."

Clinical • IO biomarker • Virus specific T cells • Duchenne Muscular Dystrophy • Epstein-Barr Virus Infections • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Identifying Muscle Stem Cell Tropic AAV Variants through Directed Evolution (ASGCT 2024) - "We are developing gene delivery vehicles that target Muscle Stem Cells rather than just Skeletal Muscle, to achieve a durable treatment. We are testing this modified gene delivery vehicle to determine if a more durable treatment for DMD can be achieved."

Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Characterization of rAAV Genomic Integrity by Long-Read Sequencing of AAV9-MyoDys45-55, a Gene Editing Therapy for Duchenne Muscular Dystrophy (ASGCT 2024) - "This work allows us to assess how well the therapy is being packaged into the carrier, if there are any missing pieces, and if there is any contamination. These learnings are critical to enhance our understanding of the packaging and delivery of this gene editing therapy for Duchenne, which offers revolutionary potential for treating this devastating disease."

Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Innate and adaptive AAV-mediated immune responses in a mouse model of Duchenne muscular dystrophy. (PubMed, Mol Ther Methods Clin Dev) - "Single-cell RNA sequencing of peripheral blood mononuclear cells confirmed that activated monocytes were a primary source of pro-inflammatory cytokines and chemokines, which were significantly increased after a second AAV9 exposure. The same activated monocyte clusters expressed both Fcγ and complement receptors, suggesting that anti-AAV-mediated activation of myeloid cells through Fcγ receptors and/or complement receptors is one mechanism by which anti-AAV antigen complexes may prime antigen-presenting cells and amplify downstream immunity."

Journal • Preclinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Nanoparticles systemically biodistribute to regenerating skeletal muscle in DMD. (PubMed, J Nanobiotechnology) - "To demonstrate, muscle regeneration regulated MSNP distribution, we experimentally induced regeneration using barium chloride which resulted in a threefold increase of intravenously injected MSNPs to sites of regeneration 7 days after injury. These discoveries provide the first evidence that nanoparticles have selective biodistribution to skeletal muscle in DMD to areas of active regeneration and that nanoparticles could enable diagnostic and selective drug delivery in DMD skeletal muscle."

Journal • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Inflammation • Muscular Dystrophy