Long-term treatment may preserve motor function in SMA, study finds
Results apply to SMA types 2 and 3; findings for type 1 remained inconclusive
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Long-term treatment with Spinraza (nusinersen) was associated with early improvements in motor function followed by long-term stability in people with spinal muscular atrophy (SMA) types 2 and 3, according to a real-world study in Turkey.
After an average follow-up of more than four years, 75% of patients with these SMA types still showed clinically meaningful improvements in motor function. However, outcomes varied among patients with SMA type 1, and researchers could not draw firm conclusions about treatment benefits because the group was small and patients had advanced disease.
“Even modest improvements or the halting of decline should be recognized as a primary clinical endpoint in patients with long-standing disease,” the researchers wrote. “Our results corroborate previous real-world evidence demonstrating early functional gains followed by a plateau phase under [Spinraza] treatment.”
The study, “Long-term real-world outcomes of nusinersen treatment in patients with spinal muscular atrophy types I–III,” was published in Brain and Development.
How Spinraza works to treat spinal muscular atrophy
SMA is primarily caused by mutations in the SMN1 gene that lead to a shortage of a protein called survival motor neuron (SMN). This protein is essential for the health of motor neurons, the nerve cells that control movement.
The number of copies of a second gene, called SMN2, also helps determine how severe SMA is. This gene can produce small amounts of working SMN protein. Generally, more SMN2 copies mean milder disease.
Spinraza, marketed by Biogen, is an approved treatment given by injection into the spinal canal. It works by changing how genetic instructions from SMN2 are processed, allowing the body to produce more working SMN protein.
Although clinical trials have shown that Spinraza is effective, long-term data from adolescents and adults treated outside clinical trials are still needed to better understand its benefits over time.
To help address this gap, researchers at Istanbul University in Turkey analyzed medical records from 25 patients with SMA types 1, 2, and 3 who received Spinraza between 2017 and 2024. “This study aims to present the long-term (over 4 years) treatment responses and follow-up outcomes of SMA patients receiving nusinersen therapy in our clinic. By focusing on dose-dependent trajectories, we evaluate whether early functional gains are sustained and how the ‘plateau phase’ reflects the therapeutic ceiling in advanced SMA,” they wrote.
Motor improvements with Spinraza sustained over four years
Twenty patients had SMA type 2 or 3 (mean age 18.9 years; nine female and 11 male patients). They were followed for an average of 51.3 months, or slightly more than four years, and had received about 13 Spinraza doses by their final evaluation.
Motor function was measured using the Hammersmith Functional Motor Scale–Expanded (HFMSE), with higher scores indicating better motor abilities.
Among 11 patients with SMA type 2, average HFMSE scores rose from 11.3 before treatment to 14.1 after the fourth dose and remained relatively stable, reaching 14.7 at the final follow-up.
Among nine patients with SMA type 3, average scores rose from 38.8 before treatment to 43 after the fourth dose and 44.1 at the final follow-up.
Statistical analyses showed a significant association between the total number of Spinraza doses received and improved HFMSE scores. Gains were most apparent during the first eight to 12 doses, after which the rate of improvement generally slowed and average motor function remained relatively stable.
After the first four doses, known as loading doses, 80% of patients with SMA types 2 and 3 showed clinically meaningful improvement, defined as a gain of at least three points on the HFMSE.
At the final follow-up, 75% still showed clinically meaningful gains, while 15% had stable motor function and 10% showed smaller improvements.
Spinraza outcomes varied among patients with SMA type 1
Five patients had SMA type 1, a more severe form of the disease. All needed breathing support from invasive mechanical ventilators and feeding tubes to receive nutrition.
Three patients died from respiratory infections during the study. Two died before receiving all four loading doses of Spinraza, while the third had shown a small improvement in motor function.
One patient who started treatment at age 1 showed substantial improvement in motor function after 13 doses. The fifth patient was no longer followed at the study center after the initial evaluation.
The researchers noted several limitations, including the small number of patients and the study’s retrospective design, which meant analyzing existing medical records. They also lacked detailed assessments of breathing function and patient-reported outcomes.
“In conclusion, our findings support that [Spinraza] leads to early functional gains followed by sustained stabilization in late-onset SMA,” the team wrote. “Future studies focusing on treatment transitions, such as switching to oral therapies, will be essential to further individualize SMA management in the era of expanding therapeutic options.”
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