To evaluate pretreatment NfL levels against disease characteristics in individuals with SMA and understand longitudinal changes of NfL in a subgroup not accessing immediate treatment.
Approach:
Study Design: Prospective cross-sectional and longitudinal cohort study conducted at Sydney Children's Hospitals Network.
Participants: Included individuals with biallelic deletions of exon 7 on SMN1, excluding those receiving treatment or with comorbid conditions affecting NfL levels.
Recruitment: Participants were recruited from June 20, 2018, to October 30, 2024, including those identified through newborn screening and clinical referrals.
Assessments: NfL concentrations in CSF and serum were measured using the Quanterix Simoa HD-X analyzer, with demographic and clinical data collected from medical records.
Key Findings:
NfL levels are significantly higher in children with SMA compared to typically developing peers.
NfL correlates with disease severity and suppression is associated with SMN protein repletion.
There is a lack of data on NfL in newborns screened for SMA, with only five neonates described internationally.
Interpretation:
Limitations:
Limited data on NfL in newborns and variability in NfL levels among individuals with different SMN2 copy numbers.
The study population may not fully represent the heterogeneity of SMA due to exclusion criteria.
by Arlene D'Silva, Karen Herbert, Lakshmi Balaji, Jia Mei He, Tejaswi Kandula, Hugo A. Sampaio, Hooi-Ling Teoh, Esther Tantsis, Jihee Sohn, Nancy Briggs, Nickson Ning, Matthew C. Kiernan, Didu S. Kariyawasam, Michelle A. Farrar
