Abstract Details

Title Serum Neurofilament Light Chain as a Potential Biomarker for Spinal Muscular Atrophy Type I Disease Activity and Therapy Response

Topic Child Neurology and Developmental Neurology

Presentation(s) S25 - Child Neurology: Spinal Muscular Atrophy: Treatments and Outcomes (2:28 PM-2:39 PM)

Poster/Presentation
Number 009

Objective To assess the relevance of serum neurofilament light chain (NfL) as a potential biomarker for spinal muscular atrophy (SMA) Type I disease activity and therapy response.

Background NfL is a sensitive, blood-based marker that can identify patients with neurodegenerative diseases, aid in the prediction of their long-term outcomes, and be used for assessing effects of treatment. At present, little is known about serum NfL levels in patients with SMA.

Design/Methods Baseline serum NfL levels were assessed by using Single Molecule Array (Simoa) technology 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, a small-molecule RNA splicing modulator. Consecutive samples were collected at the end of a respective 13-week treatment cycle period when available.

Results 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 year (1.7-22.9 pg/mL, n=21) years of age. There was also an inverse correlation between pre-treatment NfL levels and CHOP INTEND scores, a measure of motor skills. NfL levels decreased and approached normality within the first 13-week treatment period under branaplam. After 26 weeks of treatment, 3 of 4 patients with samples available for analysis showed NfL levels within the range of 1-4 year old healthy pediatric subjects.

Conclusions These results suggest that pre-treatment serum NfL levels differentiate patients with SMA Type I from healthy subjects and may be correlated with one measure of motor skills. 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.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Diethilde Theil, DVM	No disclosure on file
	No disclosure on file
Herve Jullien De Pommerol	No disclosure on file
Algirdas Kakarieka	No disclosure on file

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