Newborn screening, early treatment show benefit in SMA type 1
Babies in Turkey who were screened had better outcomes, study finds
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- Infants with SMA type 1 who were diagnosed through newborn screening and treated early with Spinraza showed better survival rates and motor function, a study found.
- These babies were also more likely to be able to eat and breathe without support.
- Newborn screening programs successfully detect SMA early, enabling timely intervention before the onset of clinical symptoms.
Infants diagnosed with spinal muscular atrophy (SMA) type 1 through newborn screening programs (NBS) and treated early with Spinraza (nusinersen) showed better survival, motor function, milestone achievement, and feeding and breathing independence than infants who began treatment after symptoms appeared, a real-world study in Turkey found.
The nationwide study’s findings demonstrate that “timing is a key determinant influencing clinical outcomes and support the implementation of national NBS as a standard of care in SMA management,” the authors wrote.
The study, “Effects of newborn screening and nusinersen on survival and functional outcomes in spinal muscular atrophy with two SMN2 copies: A nationwide multicentre real-world study from Turkey,” was published in the European Journal of Paediatric Neurology.
SMA is caused mainly by mutations in the SMN1 gene, which leads to the progressive loss of the nerve cells that control movement. A second gene, SMN2, can partially compensate for the loss of SMN1 function, with the number of SMN2 copies influencing disease severity.
Infants with two SMN2 copies typically develop SMA type 1, a severe form of the disease. It’s marked by early muscle weakness that affects movement, swallowing, and breathing. Before the availability of disease-modifying therapies, this form of SMA was the leading genetic cause of death in infancy.
Turkey program began in 2022
In May 2022, Turkey launched a national NBS program to test for SMA. These programs allow infants to receive treatment before symptoms emerge, which can alter the disease course and lead to near-normal motor milestones and improved survival.
To confirm the benefits of NBS, researchers across Turkey compared real-world outcomes of a large population of infants treated after newborn screening with those of a historical group treated after symptom onset.
The team focused on 258 infants with two SMN2 copies who received Biogen‘s Spinraza, an approved SMA injection therapy designed to increase production of working SMN protein from SMN2. Ninety-six of them were identified through SMA screening programs. Outcomes included survival, motor milestones, and the need for feeding and nutrition.
Results revealed that screening for SMA markedly shortened the time to SMA diagnosis and treatment. The infants in the screening group received an SMA diagnosis at a mean age of 18 days, compared with 146.2 days (nearly 5 months) in the historical group. Treatment began at a mean age of 43.2 days after screening and at 185 days (six months) after symptom onset.
As a result, 81.3% of screened infants began treatment before showing symptoms, compared with 1.2% in the pre-screening group. By the end of the study period, about five times more infants in the historical group had died compared with the screening group (30.9% vs. 6.3%).
All infants who began treatment before symptom onset were alive by the end of the study period. By contrast, survival gradually declined among those with symptoms at treatment initiation, which included infants in the historical group and a small subset in the screening group.
The authors noted that a death rate of 6.3% after screening suggested that Spinraza treatment may not fully address the most aggressive cases of SMA. And a mean gap of 25.2 days between diagnosis and treatment after screening exceeded the 14- to 21-day recommended window in current guidelines. They attributed this delay to real-world factors such as referrer pathways and administrative procedures.
At the start of treatment, infants in the screening group showed stronger motor function than those in the other group, as indicated by a higher mean CHOP-INTEND score (35.5 points vs. 19.4 points). CHOP-INTEND is a standardized test of infant muscle strength and movement, with higher scores reflecting stronger motor function.
While both groups showed steady improvement over time with treatment, infants diagnosed through screening maintained higher CHOP-INTEND scores at every measured time point. For example, by dose 11, the screening group showed a mean of 59 points, whereas the pre-screening group plateaued at 42.2 points.
These functional gains aligned with developmental milestones, assessed according to World Health Organization criteria. More infants in the screening group achieved independent sitting (80.7% vs. 28.4%), independent standing (64.1% vs. 14.8%), and independent walking (48.3% vs. 8.6%), with the last being the most difficult milestone to reach in this form of SMA, the team noted.
Similarly, more infants in the screening group could still be fed entirely by mouth (85.4% vs. 38.3%) than those in the historical group, more than half (61.1%) of whom had become dependent on a feeding tube. And more screened infants were still breathing without support at the last follow-up (85.4% vs. 38.3%). Nearly five times as many infants in the historical group required a tracheostomy and mechanical ventilation as in the screening group (38.9% vs. 8.3%).
“The future of SMA management will likely focus on optimising the speed of this process and exploring combination therapies to address the remaining unmet needs of the most severe [characteristics] within the disease spectrum,” the researchers wrote.
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