Level of circulating neurofilaments as a biomarker of spinal muscular atrophy during gene therapy with onasemnogene abeparvovec

The aim of the study is to analyze all current data on the role of the level of circulating neurofilament as a biomarker for spinal muscular atrophy (SMA) during gene therapy with onasemnogene abeparvovec. SMA is an orphan, inherited autosomal recessive disorder caused by defects in the SMN1 gene, which encodes the SMN protein. SMA is characterized by the loss of alpha motor neurons in the spinal cord, leading to progressive muscle weakness. Onasemnogene abeparvovec is a gene therapy aimed at restoring SMN protein expression in SMA. The review emphasizes the need to develop a panel of biomarkers to assess the severity of SMA and the effectiveness of therapy, as clinical methods are often insufficiently sensitive for monitoring treatment response. Neurofilaments, structural proteins of axons released during neuronal damage are considered promising biomarkers reflecting the degree of neurodegeneration and disease course. However, to date, the number of studies examining the use of circulating neurofilaments in SMA therapy with onasemnogene abeparvovec is limited, requiring further clinical and laboratory studies to confirm their significance. This review systematizes existing data on the molecular genetic basis of SMA pathogenesis, current treatments, and the potential of neurofilaments as biomarkers in gene therapy with onasemnogene abeparvovec. It concludes that further research in this area is needed to optimize a personalized approach to treating patients with SMA.

Contribution:
Chudakova D.A. — concept, material collection and data processing, review of publications on the topic, writing the text, article editing;
Uvakina E.V. — concept and design of the article, review of publications on the topic, writing the text, article editing.
All co-authors — approval of the final version of the manuscript, responsibility for the integrity of all parts of the manuscript.

Funding. The work was carried out as part of the implementation of the state task and the research work “Study of the etiological features of rare diseases with pathogenetic therapy” № 1220032300501-0.

Conflict of interest. The authors declare no conflict of interest.

Received: September 2, 2025
Accepted: September 16, 2025
Published: October 31, 2025

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