Neurofilament light chain as a prognostic marker in cerebral adrenoleukodystrophy.

Cerebral adrenoleukodystrophy (C-ALD) is a rapidly progressing inflammatory neurodegenerative disease with unpredictable onset in males with ALD. It must be treated at an early stage of demyelination, determined by MRI, to preserve neurocognitive function. Validation of biochemical markers that can aid in the prediction of functional outcomes is needed for optimizing disease management and therapeutic development. Our objective was to determine whether plasma neurofilament light chain (NfL), a biomarker of neuroaxonal injury, corresponds to functional outcomes after standard of care treatment with haematopoietic stem cell transplantation (HSCT). This retrospective observational cohort study of 27 patients with C-ALD treated with HSCT at a mean age of 8.0 years (standard deviation = 2.6) examined pre-treatment biomarker levels and neurocognitive outcomes 1 year after treatment. Plasma biospecimens were collected at a median of 10 days prior to HSCT, and NfL concentrations were measured with Single-Molecule Array (SiMoA) assay. White matter lesions were characterized by Loes MRI severity scores. Following treatment, neurocognitive outcomes across six domains were measured at a median of 1 year post-HSCT using the Wechsler intelligence quotient (IQ) scales, the Beery-Buktenica Test of Visual-Motor Integration and the Purdue Pegboard test. Pre-HSCT NfL values in C-ALD patients ranged from 5.0 to 911.0 pg/ml, with a median of 35.8 pg/ml. Higher NfL levels were associated with lower post-HSCT scores across all neurocognitive domains (P < 0.05). Large effect sizes were seen for visual reasoning, processing speed, fine motor dexterity and visual-motor integration (Pearson correlations: r = -0.74 to -0.84). Partial correlations showed a moderate association between NfL and neurocognitive outcomes, even when adjusting for MRI severity scores. NfL has a strong correlation with neurocognitive status following treatment for C-ALD. These encouraging findings suggest an opportunity to improve our capacity to forecast outcomes and therefore improve counselling for families considering cellular therapies.