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

被引:6
作者
Trifunov, Selena [1 ,6 ]
Natera-de Benito, Daniel [1 ,2 ]
Carrera-Garcia, Laura [1 ,2 ]
Codina, Anna [1 ]
Exposito-Escudero, Jesica [1 ,2 ]
Ortez, Carlos [1 ]
Medina, Julita [4 ]
Torres Alcala, Soraya [3 ]
Bernal, Sara [5 ,6 ]
Alias, Laura [5 ,6 ]
Badosa, Carmen [1 ]
Balsells, Sol [7 ]
Alcolea, Daniel [3 ]
Nascimento, Andres [1 ,2 ,6 ]
Jimenez-Mallebrera, Cecilia [1 ,6 ,8 ]
机构
[1] Inst Recerca St Joan De Deu, Appl Res Neuromuscular Dis, Barcelona, Spain
[2] Hosp San Juan Dios, Dept Neurol, Neuromuscular Unit, Barcelona, Spain
[3] Univ Autonoma Barcelona, Inst Invest Biomed St Pau Hosp St Pau, Hosp Santa Creu & St Pau, Dept Neurol, Barcelona, Spain
[4] Hosp St Joan De Deu, Rehabil & Phys Unit Dept, Barcelona, Spain
[5] Univ Autonoma Barcelona, Inst Invest Biomed St Pau Hosp St Pau, Dept Genet, Barcelona, Spain
[6] Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Madrid, Spain
[7] Inst Recerca St Joan De Deu, Stat Dept, Barcelona, Spain
[8] Univ Barcelona, Dept Genet Microbiol & Stat, Barcelona, Spain
关键词
Biomarkers; cerebrospinal fluid; nusinersen; response predictors; serum; spinal muscular atrophy; SHAM CONTROL; EXPRESSION; EXOSOMES;
D O I
10.3233/JND-230012
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:653 / 665
页数:13
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