Spinraza improves motor function in SMA children after loading doses
Treatment starts with 3 doses every 14 days and a fourth 30 days later
The motor function of children with spinal muscular atrophy (SMA) improves significantly in the early stages of treatment with Spinraza (nusinersen), namely within its two-month loading dose period, a study reported.
No changes in nutritional status — as assessed by weight — were seen then, however, likely because of the short follow-up period, the researchers said. Longer follow-up studies are needed to understand the impact of Spinraza on nutritional status, they said in the study, “Assessment of motor function and nutritional status in children with spinal muscular atrophy treated with nusinersen after loading period in Western China: a retrospective study,” which was published in BMC Neurology.
SMA is caused by the gradual loss of motor neurons — the nerve cells that control voluntary muscle movements — leading to symptoms such as muscle weakness and impaired motor function. The disease is also associated with feeding problems and changes in energy metabolism, nutritional status, and body composition.
Spinraza is a disease-modifying therapy designed to preserve motor neuron and muscle function. Administered directly into the spinal canal (intrathecal injection), it’s approved for all patients with the main SMA types, regardless of age or body weight.
Treatment starts with four loading doses: three doses every 14 days and the fourth 30 days later. Patients are then treated three times a year as part of a maintenance regimen.
The researchers noted, however, that no clinical studies have looked at improvements in motor function and nutritional status after the treatment’s loading period.
To assess the impact of Spinraza on motor function and nutritional status in SMA children immediately after the first four loading doses, they collected data on on 46 patients (26 girls, 20 boys) who received their loading doses at the West China Second University Hospital and The Second Affiliated Hospital of Xi’an Jiaotong University between October 2019 and March 2022.
Motor function gains after Spinraza treatment
Eight were diagnosed with SMA type 1, 31 with type 2, and seven type 3. Two participants (4.3%) had swallowing difficulties, but didn’t need a feeding tube and all those with SMA type 1 and 2 and most with type 3 reported tongue fasciculations (muscle twitches).
Motor function before treatment and after all loading doses was assessed using standard tools, including the Hammersmith Infant Neurologic Examination-Part 2 (HINE-2), the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), the Hammersmith Functional Motor Scales Expanded (HFMSE), and the Revised Upper Limb Module (RULM). The scale used in each patient depended on their age and motor function.
Motor function with SMA type 1 improved after all loading doses compared with before treatment (baseline). These changes were not statistically significant, however. According to World Health Organization (WHO) motor milestones classification, the ability to sit without support also improved.
The average motor performance of SMA type 2 patients significantly improved after the loading doses. Loading dose benefits also extended to WHO milestones for sitting independently and crawling.
Among SMA type 3 participants, only those assessed with RULM improved significantly, by 3.4 points, after all loading doses. Five patients assessed by HFMSE and five assessed with the distance walked in six minutes showed nonsignificant improvements.
To assess nutritional status, researchers applied weight per age Z-scores (WAZ), meaning the differences in the weight of SMA children compared with that of healthy children OF the same age. Across all SMA types, average WAZ scores were generally lower than healthy children, with SMA type 1 patients showing the largest differences.
Although SMA type 2 patients showed a significant average decline in WAZ scores, meaning their weight was closer to healthy people of the same age, no significant differences were seen in SMA type 1 and 3.
“A few patients showed improved nutritional status after proper nutritional management. However, due to the short follow-up time, the overall improvement in nutritional status was not statistically significant,” the researchers said, adding further studies with long follow-ups will offer a better idea about what’s causing weight problems among patients.
Of the 18 side effects related to the intrathecal administration of Spinraza, none were serious. Mild side effects were reported in 19 (41.3%) participants, mostly after the first injections. Upper airway infection and vomiting were the most common side effects.
“We showed that [Spinraza] was effective against SMA type 1, 2, and 3 after 2 months of loading period treatment,” the researchers said. “Our findings on the outcomes of patients with SMA treated with [Spinraza] can provide a better understanding of the disease, contribute to improved clinical and nutritional management of patients, and add to the assessment of disease-modifying treatment effects on SMA.”
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