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Biomarkers predicting motor function in SMA

Presented by
Prof. Valeria Sansone, University of Milano, Italy
EAN 2020
Phase 2, NURTURE
Cerebrospinal fluid (CSF) and plasma phosphorylated neurofilament heavy chain (pNfH) levels following nusinersen loading may predict future motor function in participants of the phase 2 study NURTURE [1]. This ongoing open-label study is examining the efficacy and safety of intrathecal nusinersen in presymptomatic infants with 2 or 3 copies of the SMN2 gene.

The study enrolled 25 clinically presymptomatic infants that were genetically diagnosed with spinal muscular atrophy (SMA) (15 had 2 copies of SMN2, 10 had 3 copies). All were ‚ȧ6 weeks old when treatment was initiated. CSF samples were collected at baseline, on days 1, 15, 29, 64, and 183, and every subsequent 119 days. The samples were used to measure levels of pNfH, which were correlated with Hammersmith Infant Neurological Examination (HINE)-2 motor milestone total score and WHO motor milestone walking alone. The ongoing study's primary endpoint is time to death or respiratory intervention (invasive/non-invasive ventilation for ‚Č•6 hours/day continuously for ‚Č•7 days or tracheostomy).

The median age at last visit was 34.8 months (range 25.7-45.4). All the infants were alive and none required permanent ventilation. CSF pNfH levels rapidly declined during the nusinersen loading period and then stabilised at lower plateau levels. CSF pNfH levels at baseline and day 64 significantly correlated with the ability to walk alone earlier (a WHO motor milestone), and with total HINE-2 score at day 302. In participants with 2 SMN2 copies, day 64 weight for age and compound muscle action potential amplitude also correlated with these outcome measures. The rate of infants achieving WHO motor milestones was unusually high for SMA types 1 and 2 (which is what they will most likely develop), many of them doing so in the normal time frame for a toddler.

    1. Sansone VA, et al. Abstract O1012, EAN 2020.

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