Full-Length SMN Transcript in Extracellular Vesicles as Biomarker in Individuals with Spinal Muscular Atrophy Type 2 Treated with Nusinersen.

Abstract

BACKGROUND:

Three therapeutic strategies have radically changed the therapeutic scenario for spinal muscular atrophy (SMA). However, therapeutic response differs between individuals. There is a need to identify biomarkers to further assess therapeutic response and to better understand which variables determine the extent of response.

METHODS:

We conducted a study using an optimized digital droplet PCR-based method for the ultra-sensitive detection of SMN transcript in serum EVs from SMA 2 individuals treated with nusinersen over 14 months. In parallel, we investigated levels of serum and CSF neurofilament heavy chain (pNF-H) in the same cohort.

RESULTS:

Expression of flSMN transcript in EVs of SMA 2 individuals prior to nusinersen was lower than in controls (0.40 vs 2.79 copies/ul; p < 0.05) and increased after 14 months of nusinersen (0.40 vs 1.11 copies/ul; p < 0.05). The increase in flSMN with nusinersen was significantly higher in younger individuals (p < 0.05). Serum pNF-h was higher in non-treated individuals with SMA 2 than in controls (230.72 vs 22.88 pg/ml; p < 0.05) and decreased with nusinersen (45.72 pg/ml at 6 months, 39.02 pg/ml at 14 months). CSF pNF-h in SMA 2 individuals also decreased with nusinersen (248.04 pg/ml prior to treatment, 197.10 pg/dl at 2 months, 104.43 pg/dl at 6 months, 131.03 pg/dl at 14 months).

CONCLUSIONS:

We identified an increase of flSMN transcript in serum EVs of SMA 2 individuals treated with nusinersen that was more pronounced in the younger individuals. Our results indicate that flSMN transcript expression in serum EVs is a possible biomarker in SMA to predict or monitor the response to treatment.

• Authors: Selena Trifunov, Daniel Natera-de Benito, Laura Carrera-García, Anna Codina, Jesica Expósito-Escudero, Carlos Ortez, Julita Medina, Soraya Torres Alcala, Sara Bernal, Laura Alias, Carmen Badosa, Sol Balsells, Daniel Alcolea, Andres Nascimento, Cecilia Jimenez-Mallebrera
• Journal: Journal of neuromuscular diseases (J Neuromuscul Dis) Vol. 10 Issue 4 Pg. 653-665 ( 2023) ISSN: 2214-3602 [Electronic] Netherlands
• PMID: 37038823 (Publication Type: Journal Article)

Chemical References

• nusinersen
• Biomarkers

Topics

• Humans
• Spinal Muscular Atrophies of Childhood (drug therapy)
• Muscular Atrophy, Spinal (drug therapy, genetics)
• Biomarkers
• Extracellular Vesicles