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Nusinersen-Related Improvements in Motor Function Correlate With Reduced Autophagy Markers of Spinal Muscular Atrophy
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Key Takeaways
- Nusinersen treatment in SMA patients showed reduced levels of LC3 and ATG7 proteins, correlating with improved motor function scores.
- The study suggests decreased autophagic activity may reduce SMN protein degradation, offering potential therapeutic benefits.
Findings suggest a potential correlation between motor function improvement and decreased autophagy-related protein levels in patients with spinal muscular atrophy treated with nusinersen.
Ayşe Sarılar, MD
(Credit: ResearchGate)
In a newly presented study at the 2025 Peripheral Nerve Society (PNS) Annual Meeting, held May 17-20, in Edinburgh, Scotland, investigators reported that nusinersen (Spinraza; Biogen), an FDA-approved treatment for patients with spinal muscular atrophy (SMA), was associated with reduced levels of certain autophagy-related proteins that correlated with improvements in motor function scores.1
The study assessed 16 patients with SMA (Type 2, n = 4; Type 3, n =12), all of whom had homozygous SMN1 mutations or deletions and at least 3 copies of SMN2. Cerebrospinal fluid samples were collected before treatment and after each of the 4 nusinersen loading doses given to patients. Researchers measured levels of the autophagy-related proteins LC3, Beclin, ATG7, and p62 using ELISA and correlated them with Hammersmith Functional Motor Scale–Expanded (HFMSE) scores.
Presented by lead author Ayşe Sarılar, MD, professor in the Department of Neurology at Erciyes University School of Medicine in Turkey, the study population had a mean age of 37.81 years (± 8.61), and 56.2% of the patients included were men. No significant differences were observed in levels of LC3, Beclin, ATG7, or p62 before and after treatment. However, researchers reported a negative correlation between improvements in HFMSE scores and levels of LC3 and ATG7, suggesting a reduction in these markers as motor function improved.
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The authors concluded that the reduction in LC3 and ATG7 levels during treatment may reflect decreased autophagic activity, which could potentially reduce SMN protein degradation. The findings potentially support the idea that autophagy plays a role in SMA progression and that targeting this cellular process might offer therapeutic benefit. The investigators noted that further research may be needed to confirm these findings and clarify the role of autophagy as a biological marker in SMA.
Nusinersen was the first FDA-approved drug for the treatment of SMA in pediatric and adult patients in December 2016.2 The drug is an antisense oligonucleotide that targets the root cause of SMA by continuously increasing the amount of full-length SMN protein produced in the body. It is administered directly into the central nervous system, where motor neurons reside, to deliver treatment where the disease starts.
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