Infants diagnosed with spinal muscular atrophy (SMA) who received Zolgensma within their first six weeks of life showed better motor, respiratory, and nutritional outcomes, according to a European study.
While all age groups up to 24 months experienced significant improvements in motor function after treatment, these improvements were less pronounced in older children.
Administering Zolgensma earlier in life was associated with fewer liver-related side effects, particularly in patients under 8 months of age.
The study, published in The Lancet Regional Health – Europe, emphasized, “Treatment at or before six weeks of age is the most influential factor for motor development and achieving milestones.”
Understanding SMA and Zolgensma’s Role
SMA is primarily caused by mutations in the SMN1 gene, which results in minimal to no production of SMN protein. This condition leads to the progressive degeneration of motor neurons, resulting in symptoms such as muscle weakness and wasting.
Zolgensma (onasemnogene abeparvovec-xioi) is a one-time gene therapy designed to deliver functional copies of the SMN1 gene to cells, allowing for the production of SMN protein.
Study Highlights
Researchers from Germany, Austria, and Switzerland analyzed data from 343 SMA patients treated with Zolgensma, encompassing both symptomatic and presymptomatic cases. The average follow-up period was 13.8 months, and the average treatment age was 14 months. Approximately 23% of the participants were presymptomatic at the time of treatment, while the rest had varying levels of symptom severity and SMA types.
Motor function outcomes were assessed in relation to the age at treatment and the number of SMN2 gene copies. The SMN2 gene produces limited amounts of SMN protein and partially compensates for SMN1 mutations. In this study, 40% of participants had three copies of SMN2, while others had the standard two copies.
Key Findings
- Early Treatment Yields Better Motor Function:
Infants treated within six weeks of birth demonstrated the most significant improvements in motor skills. Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores were consistently higher for younger patients. Those treated after two years of age did not exhibit motor improvements, although their scores remained stable. - Milestone Achievement in Presymptomatic Infants:
- 43% achieved independent sitting.
- 78% achieved standing.
- 74% achieved walking within typical age ranges.
In contrast, fewer than 10% of children treated after the onset of symptoms reached these milestones.
- Impact of SMN2 Copies:
Patients with three copies of SMN2 demonstrated better motor outcomes and were more likely to achieve milestones like standing and walking independently compared to those with two copies. A greater number of SMN2 copies also correlated with reduced dependence on respiratory and nutritional support. - Reduced Side Effects in Younger Patients:
Among the 123 patients who experienced 263 adverse events, liver-related complications were more common in those treated after 8 months of age. Other side effects, such as fever, elevated heart enzymes, and vomiting, occurred consistently across age groups.
Importance of Newborn Screening
This research highlights the need for newborn screening programs to enable timely diagnosis and early intervention for SMA, particularly for infants at risk of early disease onset. Early identification ensures that treatment can begin during the optimal window for achieving the best outcomes.
Expert Commentary
Laurent Servais, MD, PhD, from the University of Oxford and the University of Liège, commended the study for its comprehensive analysis of a large, diverse patient population. He noted that this data provides critical insights into treatment outcomes for groups often excluded from industry-funded clinical trials, such as older children. However, he emphasized the necessity for extended follow-up to better understand long-term treatment effects.
This study reinforces the significance of prompt intervention and underscores the potential benefits of gene therapy for SMA, particularly when delivered early in life.