7 SMA children with symptoms show motor gains after gene therapy
But findings of real-world study emphasize importance of early diagnosis
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- Children with symptomatic SMA experienced gains in motor function gains after receiving the one-time gene therapy Zolgensma.
- These findings add to much-needed real-world data on the use of gene therapy after symptom onset.
- The results also underscore the critical importance of early diagnosis of SMA for improving outcomes among children.
Children with spinal muscular atrophy (SMA) already living with symptoms experienced gains in motor abilities after receiving the gene therapy Zolgensma (onasemnogene abeparvovec-xioi), a small Brazilian study found.
The real-world report tracked the outcomes of seven youngsters in the South American nation who were treated with Zolgensma only after the onset of symptoms — patients often excluded from clinical trials testing a treatment’s potential benefits prior to regulatory approval. Such trial restrictions “[limit] the extrapolation of results to real-world clinical practice, especially in middle-income countries where treatment is frequently initiated well after symptom onset.”
The results of this study showed that all six children with SMA type 1 maintained head control and most achieved independent sitting. The single child with SMA type 2 gained the ability to walk independently, the data demonstrated.
According to the researchers, these improvements “align with previous real-world data from larger registries, … which similarly note that … gene therapy [after symptom onset] modifies the clinical course [of SMA,] leading to functional stabilization” where disease progression would typically occur.
The team noted, however, that many of these youngsters continued to need breathing and feeding support, and some received other SMA treatments after the gene therapy.
“These results emphasize the need for realistic treatment counseling and reinforce the importance of early diagnosis,” the researchers wrote.
The study, “Gene therapy benefits in a small cohort of symptomatic 5q spinal muscular atrophy patients and real world pediatric outcomes,” was published in Jornal de Pediatria.
SMA is chiefly caused by mutations in the SMN1 gene, which result in a deficiency of the survival motor neuron (SMN) protein and progressive loss of motor neurons, the specialized nerve cells that control movement. This can lead to symptoms such as muscle weakness, difficulties with swallowing, and breathing problems. Most children with the disease do not achieve motor milestones.
Treatment of SMA has changed substantially in recent years with the introduction of disease-modifying therapies, including Zolgensma. The gene therapy delivers a functional copy of the SMN1 gene using a viral vector, with studies suggesting maximal clinical benefit when treatment is given early in the disease course.
However, clinical trials testing Zolgensma typically enrolled highly selective groups of participants, making it difficult to know whether their findings apply to children treated in routine clinical practice. This is particularly relevant in countries with lower incomes and more limited treatment access, where gene therapy may not be readily available.
5 of 6 with SMA type 1 able to sit independently after Zolgensma
To learn more, the researchers followed seven children with two SMA types, all treated at a single center, who received Zolgensma between March 2024 and June 2025. Five of the children were girls.
Symptom onset had occurred before 6 months of age in the children with SMA type 1. In the child with SMA type 2, symptoms began between 12 and 15 months of age. The most frequent initial manifestations were low muscle tone, seen in 71%, muscle weakness, experienced by 57%, and delayed motor development, seen for 43%. Nearly half of the children had swallowing difficulties.
Among the six with SMA type 1, all maintained head control and gained the ability to sit with support, with five (83%) eventually sitting on their own. The child with SMA type 2 experienced broader functional gains and eventually walked independently.
Therapeutic expectations must remain realistic when treatment begins after symptom onset.
Six children (86%) required noninvasive ventilation after treatment, while the number of children with a tracheostomy increased from one to two because of a respiratory complication. Tracheostomy is a surgically created opening into the windpipe to help with breathing.
Before treatment, four children (57%) received nutrition through a feeding tube, with one child able to take some food by mouth. During follow-up, one child was able to eat exclusively by mouth, while four were able to combine oral feeding with tube feeding.
All seven children had previously received the approved SMA treatment Spinraza (nusinersen), typically given every four months after loading doses. Among these children, the number of doses before gene therapy ranged from three to eight. During follow-up, three children started Evrysdi (risdiplam), another SMA treatment, and one restarted Spinraza.
Overall, treatment with Zolgensma showed benefits for all of the children, the researchers noted. However, the team stressed that, even with gene therapy, “therapeutic expectations must remain realistic when treatment begins after symptom onset.”
Side effects common, though mostly mild, following gene therapy
Most children (86%) experienced at least one side effect during the first month after treatment, although most were mild or moderate. Nausea and vomiting were the most common.
Following the first month after treatment, five children needed urgent medical evaluation, most commonly for pneumonia, a type of lung infection. Four children were hospitalized due to pneumonia or respiratory failure.
According to the researchers, “these results underscore the importance of early treatment and continued multidisciplinary follow-up after infusion.”
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