There is an unmet need for blood-based biomarkers that can reliably detect MS disease activity. Recent advances in assay sensitivity have enabled quantification of promising candidates including neurofilament light chain (NfL), glial fibrillary acids protein (GFAP) and tau.

Autologous haematopoietic stem cell transplant (AHSCT) is reserved for aggressive forms of MS. Although it involves CNS-penetrating chemotherapy, it and has been shown to halt detectable CNS inflammatory activity for prolonged periods in the absence of disease-modifying drugs. Significant pre-treatment tissue damage at followed by inflammatory disease abeyance should be reflected longitudinal sera collected from these patients.

Sera were collected from 23 MS patients pre-treatment, and following AHSCT at 3, 6, 9 and 12-months in addition from 30 non-inflammatory neurological controls. Biomarker quantification was performed with the SiMoA platform.

Pre-AHSCT levels of serum NfL and GFAP but not Tau were elevated compared to controls (p=0.0001), and NfL correlated with lesion-based disease activity (6-month clinical relapse, MRI-T2 and Gadolinium-enhancement). 3-months post-treatment, while NfL levels remained elevated, Tau/GFAP paradoxically increased (p=0.0023/0.0017). These increases at 3m correlated with MRI ‘pseudoatrophy’ at 6-months reported previously. NfL/Tau levels dropped to that of controls by 6-months (p=0.0036/0.0159). GFAP levels dropped progressively after 6-months although even at 12-months remained higher than controls (p=0.004).

NfL correlates most closely with disease activity and treatment response around the time of AHSCT. Chemotherapy-related toxicity may account for transient increases in NfL, Tau and MRI brain atrophy post-ASHCT. While GFAP was higher in the MS patients than controls, it remained elevated 12-months post-treatment, perhaps indicative of astrocyte involvement in repair/remyelination.