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
相关论文
共 50 条
  • [22] Outcomes of Children Treated With Nusinersen/Onasemnogene Abeparvovec for Pediatric Spinal Muscular Atrophy Type 1
    Chacko, A.
    Sly, P. D.
    Gauld, L.
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2023, 207
  • [23] Clinical Course in a Patient With Spinal Muscular Atrophy Type 0 Treated With Nusinersen and Onasemnogene Abeparvovec
    Matesanz, Susan E.
    Curry, Candace
    Gross, Brianna
    Rubin, Adam I.
    Linn, Rebecca
    Yum, Sabrina W.
    Kichula, Elizabeth A.
    JOURNAL OF CHILD NEUROLOGY, 2020, 35 (11) : 717 - 723
  • [24] Characterization of patients with Type 1 Spinal Muscular Atrophy in advanced disease state treated with Nusinersen
    Balkenhol, J.
    Beytia, M.
    Jofre, J.
    Suarez, B.
    Hervias, C.
    Calcagno, G.
    Castiglioni, C.
    NEUROMUSCULAR DISORDERS, 2024, 43
  • [25] Age related treatment effect in type II Spinal Muscular Atrophy pediatric patients treated with nusinersen
    Coratti, Giorgia
    Pane, Marika
    Lucibello, Simona
    Pera, Maria Carmela
    Pasternak, Amy
    Montes, Jacqueline
    Sansone, Valeria A.
    Duong, Tina
    Young, Sally Dunaway
    Messina, Sonia
    D'Amico, Adele
    Civitello, Matthew
    Glanzman, Allan M.
    Bruno, Claudio
    Salmin, Francesca
    Tacchetti, Paola
    Carnicella, Sara
    Sframeli, Maria
    Antonaci, Laura
    Frongia, Anna Lia
    De Vivo, Darryl C.
    Darras, Basil T.
    Day, John
    Bertini, Enrico
    Muntoni, Francesco
    Finkel, Richard
    Mercuri, Eugenio
    NEUROMUSCULAR DISORDERS, 2021, 31 (07) : 596 - 602
  • [26] Htra2-beta1 restores full-length SMN2 expression by activating an exonic splicing enhancer; An exciting target for therapy in spinal muscular atrophy.
    Wirth, B
    Hofmann, Y
    Lorson, CL
    Stamm, S
    Androphy, EJ
    AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (04) : 10 - 10
  • [27] Surgical correction of a ventricular septal defect in a child with spinal muscular atrophy type 2 treated with nusinersen sodium: a case report
    Bicer, Mehmet
    Kozan, Sima
    Ozturk, Figen
    Akcay, Ayfer Arduc
    JOURNAL OF CARDIOTHORACIC SURGERY, 2023, 18 (01)
  • [28] Nusinersen efficacy data for 24-month in type 2 and 3 spinal muscular atrophy
    Pane, Marika
    Coratti, Giorgia
    Pera, Maria Carmela
    Sansone, Valeria A.
    Messina, Sonia
    d'Amico, Adele
    Bruno, Claudio
    Salmin, Francesca
    Albamonte, Emilio
    De Sanctis, Roberto
    Sframeli, Maria
    Di Bella, Vincenzo
    Morando, Simone
    Palermo, Concetta
    Frongia, Anna Lia
    Antonaci, Laura
    Capasso, Anna
    Catteruccia, Michela
    Longo, Antonella
    Ricci, Martina
    Cutrona, Costanza
    Pirola, Alice
    Bravetti, Chiara
    Pedemonte, Marina
    Brolatti, Noemi
    Bertini, Enrico
    Mercuri, Eugenio
    ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 2022, 9 (03): : 403 - 408
  • [29] Surgical correction of a ventricular septal defect in a child with spinal muscular atrophy type 2 treated with nusinersen sodium: a case report
    Mehmet Biçer
    Şima Kozan
    Figen Öztürk
    Ayfer Arduç Akçay
    Journal of Cardiothoracic Surgery, 18
  • [30] Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3
    Maggi, Lorenzo
    Bello, Luca
    Bonanno, Silvia
    Govoni, Alessandra
    Caponnetto, Claudia
    Passamano, Luigia
    Grandis, Marina
    Trojsi, Francesca
    Cerri, Federica
    Ferraro, Manfredi
    Bozzoni, Virginia
    Caumo, Luca
    Piras, Rachele
    Tanel, Raffaella
    Saccani, Elena
    Meneri, Megi
    Vacchiano, Veria
    Ricci, Giulia
    Soraru', Gianni
    D'Errico, Eustachio
    Tramacere, Irene
    Bortolani, Sara
    Pavesi, Giovanni
    Zanin, Riccardo
    Silvestrini, Mauro
    Politano, Luisa
    Schenone, Angelo
    Previtali, Stefano Carlo
    Berardinelli, Angela
    Turri, Mara
    Verriello, Lorenzo
    Coccia, Michela
    Mantegazza, Renato
    Liguori, Rocco
    Filosto, Massimiliano
    Marrosu, Gianni
    Siciliano, Gabriele
    Simone, Isabella Laura
    Mongini, Tiziana
    Comi, Giacomo
    Pegoraro, Elena
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2020, 91 (11): : 1166 - 1174