Objective: The European (EU) TALISMAN study will retrospectively and prospectively explore disease progression and the correlation with plasma neurofilament light chain (p-NfL) and brain MRI biomarkers in patients with multiple system atrophy (MSA), as well as the impact of MSA on patient and caregiver lives.

Background: MSA is a rare, sporadic, rapidly progressing neurodegenerative disorder [1,2]. Plasma and MRI biomarkers have the potential to be indicators of disease progression; p-NfL levels in patients with MSA correlate with disease severity (measured by the unified MSA rating scale [UMSARS]), and patients with abnormal brain MRI scans exhibit faster disease progression [3].

Method: This observational study will run in 4 countries across the EU. Approximately 60 patients with MSA aged ≥40 and ≤75 years will be enrolled. Patients must have a predicted survival of ≥3 years and a UMSARS Part I score <17 (omitting item 11) 10–18 months before baseline (BL) for inclusion in the retrospective cohort. Patients must meet these criteria at BL or have met the retrospective criteria, regardless of disease state at BL, to be eligible for the prospective cohort.

Key requirements for the retrospective cohort include p-NfL measurements, brain MRI scans and UMSARS assessments performed 10–18 months before BL. The prospective cohort must have these data collected from BL to 12 months. Results will be combined and compared with a similar prospective study running in parallel in China.

Results: Primary blood- and MRI-biomarker endpoints will be changes in p-NfL levels and change in MRI parameters, including brain volume, diffusivity and cerebral blood flow within predefined regions of interest at 10–18 months before BL, BL, 6 and 12 months. Secondary endpoints include: i) disease progression, measured retrospectively and prospectively by change in UMSARS scores; ii) level of dependency of patients; and iii) patient and caregiver quality of life. Correlation between p-NfL levels, UMSARS and MRI parameters will be evaluated to determine the relationship and predictive value for disease progression.

Conclusion: This study is designed to elucidate the role of p-NfL and brain MRI as potential biomarkers for assessing disease progression in MSA. Findings of this study can additionally clarify the thresholds for within-patient clinically meaningful change of UMSARS, and ultimately inform clinical trial design.

References: 1. Petrovic IN, Ling H, Asi Y, et al. Multiple system atrophy-parkinsonism with slow progression and prolonged survival: a diagnostic catch. Mov Disord. Aug 2012;27(9):1186-90. doi:10.1002/mds.25115
2. Fanciulli A, Wenning GK. Multiple-system atrophy. N Engl J Med. Jan 15 2015;372(3):249-63. doi:10.1056/NEJMra1311488
3. Krismer F, Seppi K, Wenning GK, et al. Abnormalities on structural MRI associate with faster disease progression in multiple system atrophy. Parkinsonism Relat Disord. Jan 2019;58:23-27.

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