Monitoring Nusinersen Treatment Effects in Children with Spinal Muscular Atrophy with Quantitative Muscle MRI

Area of Science:

• Neurology
• Biomedical Imaging
• Molecular Medicine

Background:

• Spinal muscular atrophy (SMA) is a genetic disorder characterized by a deficiency in the survival motor neuron (SMN) protein.
• Intrathecal nusinersen therapy aims to increase SMN protein levels in motor neurons, improving motor function in affected children.

Purpose of the Study:

• To investigate muscle microstructure and fat content changes during nusinersen treatment using quantitative MRI.
• To evaluate the potential of quantitative MRI as a biomarker for treatment efficacy in SMA.

Main Methods:

• A quantitative MRI protocol including DIXON, T2 mapping, and diffusion tensor imaging (DTI) was applied.
• 8 children with SMA types 2 and 3 underwent MRI scans before and after nusinersen injections (4th and 6th) within the first year.
• Muscle strength and motor function were also assessed concurrently.

Main Results:

• A significant increase in thigh muscle fat fraction was observed in most muscles during treatment.
• Diffusion tensor imaging (DTI) parameters indicated a normalization of hamstring microstructure towards healthy values.
• No significant changes were detected in T2 mapping values over the treatment period.

Conclusions:

• Nusinersen treatment in children with SMA is associated with ongoing fatty infiltration but also potential normalization of muscle microstructure.
• Quantitative muscle MRI demonstrates potential as a sensitive biomarker for assessing the therapeutic effects of nusinersen in SMA.