Background: Elevated CSF and blood neurofilament (NF) levels have been detected in neurodegenerative disorders.
Objectives: To investigate change in plasma phosphorylated NF heavy chain (pNF-H) levels over time in nusinersen trial participants with infantile- or later-onset SMA.
Approach: Individuals treated with nusinersen or sham-procedure in the Phase 3 ENDEAR and CHERISH studies could transition to the open-label SHINE extension study (NCT02594124). Plasma pNF-H levels were measured at baseline and predose using the ProteinSimple pNF-H ELLA assay.
Results: In participants who initiated nusinersen in ENDEAR and continued in SHINE (n=76), the geometric mean (±SD) plasma pNF-H concentration was 14,388 (8326) pg/ml at nusinersen initiation (ENDEAR baseline) and declined to 1261 (993) pg/ml at Day 302 (n=51; 15 October 2018 SHINE data cut). In those who received sham-procedure in ENDEAR and initiated nusinersen in SHINE (n=20), the geometric mean pNF-H concentration was 7556 (6265) pg/ml at nusinersen initiation (SHINE baseline) and declined to 778 (653) pg/ml at Day 183 (n=13). In those who received nusinersen in CHERISH and SHINE (n=83), the geometric mean plasma pNF-H concentration was 1297 (1261) pg/ml at CHERISH baseline and declined to 439 (374) pg/ml at Day 450 (n=79). In the CHERISH sham-procedure group who initiated nusinersen in SHINE (n=32), the geometric mean pNF-H concentration was 746 (676) pg/ml at SHINE baseline and declined to 382 (204) pg/ml at Day 253 (n=8). Values for later timepoints will be presented.
Conclusions: Plasma pNF-H levels at treatment initiation were higher in participants who initiated nusinersen in ENDEAR or CHERISH (compared with SHINE), consistent with differences attributable to age at treatment initiation and SMA disease characteristics. However, these data demonstrate a similar decline in pNF-H levels over time in nusinersen-treated participants, irrespective of when treatment was initiated.
Study Support: Biogen; encore submission