P.273Serum neurofilament light chain in type 1 spinal muscular atrophy: 30 months data from first part of a branaplam phase II study

Abstract

Results from patients with neurodegenerative diseases have shown that neurofilament light chain (NfL) is a sensitive, blood-based marker that can identify patients, aid in prediction of long-term outcomes, and be used to assess effects of treatment. At present, little is known about NfL levels in the blood of patients with spinal muscular atrophy (SMA). The present study assesses the relevance of serum NfL as a potential biomarker for SMA Type I disease activity and therapy response. Baseline serum NfL levels were determined in 12 patients with SMA Type I (2.2-7.6 months of age) who were enrolled in a first-in-human study of branaplam (LMI070 × 2201- NCT02268552; EudraCT number 2014-002053-19, part 1), an oral small-molecule RNA splicing modulator. Consecutive samples were collected at the end of a respective 13-week treatment cycle period when available. The range of pre-treatment NfL levels in Type I patients was 177-983 pg/mL and did not overlap with the range measured from healthy pediatric subjects with 1-4 years of age (1.7-22.9 pg/mL, n=21). There was also an inverse correlation between pre-treatment NfL levels and CHOP INTEND scores, a measure of motor skills. NfL levels decreased within the first 13-week treatment period under branaplam and reached the range of 1-4 year old healthy subjects after 26 weeks. NfL levels after at least 30 months of treatment will be presented. These results suggest that pre-treatment serum NfL levels differentiate patients with SMA Type I from healthy subjects and may be correlated with CHOP INTEND scores. Measurement of serum NfL may also be considered as a biomarker for SMA therapy response. These conclusions are limited by the small number of samples evaluated and the lack of data from healthy pediatric infants within the first year of age. The dynamic course of blood NfL levels in SMA patients requires further study.