Studying the immune system in spinal muscular atrophy before and after gene therapy

What is it about?

Spinal muscular atrophy (SMA) is a serious genetic disease that affects movement and muscle strength in babies and young children. In this study, we used advanced gene expression tools to study how the immune system behaves in SMA both before and after treatment with gene therapy. We found that some immune cells become overactive after treatment, which may affect how well children recover. These results suggest that the immune system could be an important factor in how SMA progresses and how effective treatment is. Our findings may help improve future therapies by identifying new targets to monitor or regulate immune activity.

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Photo by Bioscience Image Library by Fayette Reynolds on Unsplash

Photo by Bioscience Image Library by Fayette Reynolds on Unsplash

Why is it important?

This is the first study to apply single-cell RNA sequencing (scRNA-seq) to blood samples from infants with spinal muscular atrophy (SMA), enabling an unprecedented resolution of immune cell behavior in this devastating pediatric disease. While prior SMA research has focused primarily on motor neurons and SMN1/SMN2 gene restoration, our study shifts attention to the immune system, an underexplored yet potentially critical modifier of treatment outcomes. We not only capture immune dysregulation before symptom onset, but also identify robust post-treatment inflammatory responses that may affect recovery following gene therapy. These findings are especially timely given the recent widespread adoption of AAV-based gene therapy (e.g., Zolgensma), where clinical variability remains poorly understood. Our work has the potential to inform adjunct immunomodulatory strategies and improve monitoring protocols for infants undergoing gene therapy.