Younger children on Spinraza made more motor function gains: Study
SMA type 2 patients should begin treatment as early as possible: Researchers
Being on Spinraza (nusinersen) for up to three years results in a gain in motor function for children with spinal muscular atrophy (SMA) type 2, with the youngest children benefiting the most from treatment, a small study has found.
“It is therefore important to start the treatment as early as possible, in order to limit the natural evolution of the disease and potentiate the gain in function,” researchers wrote.
The study also found that testing compound motor action potential (CMAP) — the overall response of a muscle to a single nerve impulse — to routinely monitor patients’ progress is feasible and correlates with overall motor improvement.
SMA occurs due to mutations in the SMN1 gene, which result in little or no SMN protein being made. Without SMN, motor neurons (the nerve cells that control muscle movement) lose function and die, leading to muscle weakness and wasting, which worsen over time.
Biogen’s Spinraza, the first disease-modifying therapy to be approved for all types of SMA, increases the levels of SMN protein by acting upon a backup gene called SMN2. It is given as as injection into the spinal canal every four months, after four initial loading doses.
Now, a team of researchers reported on the use of compound motor action potential (CMAP) to monitor response to Spinraza over the course of three years in patients with SMA type 2. CMAP can record the combined electrical signals produced by muscle fibers in response to motor neuron stimulation.
“We wanted to determine whether CMAP could be a sensitive biomarker to identify the evolution or muscle decline of patients over a short period of time, which would be useful for the follow-up of children treated with [Spinraza],” the researches wrote.
The study included 10 children (six girls and four boys) with SMA type 2, ages ranging from 11 months to 10 years at the start of treatment with Spinraza. Without treatment, most children with SMA type 2 are unable to stand or walk on their own.
Motor function was evaluated using the Motor Function Measure (MFM) scale, where scores are expressed as a percentage in relation to the maximum score. Higher scores indicate better motor function.
‘Youngest patients obtained higher scores’ on MFM scale
On average, MFM scores increased by 2.04% points from before to three years after treatment. Specifically, the scores increased by 4.65% points in children younger than 5 years, and decreased by 0.57% points in those older than 5 years. However, these changes were not significant.
“Although these results were not statistically significant, we observed that the youngest patients obtained higher scores,” the researchers wrote. In contrast, MFM scores decreased in the two oldest children, ages 9 and 10 years.
Standing and transfer skills and both axial and proximal motor function and distal motor function improved in children younger than 5 years. Axial motor function involves movements of the central body, while proximal motor function refers to movements near the center of the body, such as the limbs. Distal motor function refers to movements in the outer parts of the body, such as the fingers and toes.
In children older than 5 years, however, there was no improvement in axial and proximal motor function.
“SMA is a degenerative disease, and thus after 5 years without treatment, children have already irreversibly lost motor strength and skills. Therefore, our study suggests early detection and the introduction of [Spinraza] treatment as soon as possible,” the researchers wrote.
When the team measured the average CMAP for the median nerve, which provides motor function to the forearm, wrist, and hand, it significantly increased at 22 months after treatment.
The average CMAP doubled in children younger than 5 years, and correlated with MFM scores. This means that the higher the CMAP, the higher the MFM scores, suggesting CMAP as “a sensitive biomarker that can be used in practice for the monitoring of patients.”
“This examination, which is less time consuming and more reproducible than some clinical scales, could be integrated in the follow-up of patients with SMA,” the researchers wrote.
The study suggests “a gain in motor function in children with SMA type 2. The gain was even more significant the younger the patients were treated, and particularly notable on proximal and distal motor functions,” the researchers concluded.
However, “despite these improvements, patients with SMA type 2 treated with [Spinraza] still require intensive support services and remain severely disabled. None of the patients acquired walking,” they noted.