Real-World Data in Children with Spinal Muscular Atrophy Type 1 on Long-Term Ventilation Receiving Gene Therapy: A...

Area of Science:

• Neurology
• Pulmonology
• Genetics

Background:

• Spinal muscular atrophy type 1 (SMA-1) patients requiring invasive ventilation face challenges in meeting gene therapy eligibility criteria.
• Eligibility requires tolerating at least 8 hours off ventilation daily, necessitating optimized respiratory support.
• Onasemnogene abeparvovec (Zolgensma) is a gene therapy option for SMA-1, but its use in heavily ventilated patients requires careful assessment.

Purpose of the Study:

• To evaluate the short-term safety and efficacy of onasemnogene abeparvovec (Zolgensma) gene therapy on respiratory function.
• To assess the impact of pre-gene therapy clinical management on ventilation weaning.
• To determine the effectiveness of gene therapy in SMA-1 patients ventilated via tracheostomy.

Main Methods:

• A prospective cohort study involving 22 SMA-1 patients ventilated via tracheostomy.
• Implementation of a pre-gene therapy weaning protocol including optimizing ventilator settings, cough augmentation, airway secretion management, nutritional support, and infection control.
• Administration of onasemnogene abeparvovec (Zolgensma) at a median age of 26 months, with a mean follow-up of 7.64 months.

Main Results:

• The pre-gene therapy clinical management successfully enabled 22 SMA-1 patients to tolerate at least 8 hours off ventilation daily.
• Onasemnogene abeparvovec (Zolgensma) gene therapy was safe and effective in the short term.
• Improvements were observed in resolving paradoxical breathing, enhancing cough ability, reducing airway secretions, and increasing CHOP-INTEND scores.

Conclusions:

• Optimized clinical care is crucial for enabling SMA-1 patients to meet ventilation weaning criteria for gene therapy.
• Gene therapy (onasemnogene abeparvovec; Zolgensma) demonstrates short-term safety and efficacy in improving respiratory outcomes in ventilated SMA-1 patients.
• High-quality clinical care should be integrated with gene therapy for optimal patient benefit, with long-term follow-up recommended.