Self-Assessment: Toxic Myopathies & Neuropathies | Advances in Duchenne Treatment & Management-Dr. Ciafaloni Presentation

Dr. Ciafaloni Presentation
Pdf Summary
The document is an overview of the current landscape and future potential of gene therapy (GT) in treating Duchenne Muscular Dystrophy (DMD). It highlights several key points:<br /><br />### Milestones and Challenges:<br />- **Immunity Issues:** Pre-existing and induced immunity to recombinant adeno-associated virus (rAAV) vectors, which limit the ability to re-dose patients.<br />- **Safety Concerns:** Safety is a significant focus, with strategies being developed to mitigate risks such as immune reactions, liver toxicity, and myocarditis. <br />- **Vector Improvements:** Efforts are being made to enhance vector safety and efficacy, manufacturing scale, and cost-efficiency.<br />- **Durability:** Investigating the long-term effectiveness of GT and how to overcome the dilution effect as patients grow.<br />- **Screening:** The potential role of newborn screening for DMD in the era of gene therapy to facilitate earlier diagnosis.<br /><br />### Gene Therapy Programs:<br />- **Tissue Specificity:** Emphasis on delivering therapeutic genes specifically to muscle and heart tissues using engineered viral vectors.<br />- **Promoters and Serotypes:** Companies like Regenxbio, Sarepta, Pfizer, and Solid Biosciences are using different promoters and AAV serotypes to maximize transgene expression and safety.<br /><br />### Vector Advantages and Disadvantages:<br />- **Advantages:** High transduction efficiency, no known human pathology, and the ability to target specific tissues.<br />- **Disadvantages:** Some patients may have pre-existing antibodies to AAVs, small payload capacity, and manufacturing complexities.<br /><br />### Safety and Seroconversion Issues:<br />- **Shedding and Seroconversion:** Concerns about vector shedding and the risk of seroconversion among patients and families, with ongoing studies to assess these risks.<br />- **Safety Protocols:** Various mitigation strategies being implemented to handle immune reactions and other adverse events.<br /><br />### Novel Vectors and Non-Viral Delivery:<br />- **Engineered Vectors:** Development of more potent and selective AAV capsid variants, such as MyoAAV, to enhance muscle transduction.<br />- **Exosomes:** Utilizing exosomes as non-viral delivery vessels for genetic medicines due to their natural non-immunogenic properties.<br /><br />### Newborn Screening and Diagnostic Delays:<br />- **Screening Benefits:** Early diagnosis through newborn screening may significantly improve outcomes by enabling timely intervention and reducing the psychological burden on families.<br />- **Challenges:** Ensuring broad and equitable access to screening and emerging therapies, especially considering racial and ethnic disparities in diagnosis timing.<br /><br />### Global Health Equity:<br />- **Ethical Considerations:** Addressing the challenges of providing high-cost novel therapies to patients in low-resource settings and the ethics of international travel for self-pay treatments.<br /><br />The document concludes with a call for optimizing access to new treatments and improving institutional readiness and training for healthcare providers in the complex era of gene therapy.
Keywords
gene therapy
Duchenne Muscular Dystrophy
immunity issues
safety concerns
vector improvements
newborn screening
tissue specificity
AAV serotypes
seroconversion
global health equity