Nusinersen (Spinraza®) restores the developmental trajectory of motor axons and also reduces degeneration in spinal muscular atrophy (SMA), according to a study published in the Journal of Physiology.

This was shown to especially be the case in children who started treatment early.

“Our findings move the field forward in understanding the developmental aspect of childhood-onset motor neuron diseases and changes in axonal function associated with disease modification,” Didu ST Kariyawasam and the coauthors of the study wrote.

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SMA is characterized by the degeneration of alpha motor neurons in the anterior horn of the spinal cord. Nusinersen is an antisense oligonucleotide that promotes the production of functional survival motor neuron protein from the SMN2 gene, thereby restoring levels of the protein, which is essential for the survival of motor neurons. 

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Here, a team of researchers from Australia investigated axonal changes that occur during neurodevelopment in SMA. To do so, they stimulated the median motor nerve at the wrist using nerve excitability techniques in 24 children with SMA and 71 controls of the same age.

The results showed there were significant differences in axonal development in the youngest children with SMA. These were reduced compound muscle action potential (CMAP), higher axonal threshold and rheobase, and greater changes in depolarizing and hyperpolarizing threshold electrotonus. Moreover, subexcitability increased in all children with SMA. 

Nerve excitability changes were mainly observed in young children with SMA with treatment. These changes included increases in CMAP, reduction in the axonal threshold, fanning in of threshold electrotonus, an increase in resting current-threshold slope, and a reduction in subexcitability.

“Nusinersen promotes developmental recovery of the motor axon to some extent, with nerve excitability changes suggesting radial growth, myelination of the axon, and localization of potassium ion channels to the juxtaparanode,” the researchers wrote.

They said these were similar to maturational changes that normally occur in healthy children.


Kariyawasam DS, D’Silva AM, Herbert K, et al. Axonal excitability changes in children with spinal muscular atrophy treated with nusinersen. J Physiol. Published online November 15, 2021. doi:10.1113/JP282249