Background
The heterogenous variations in the clinical disease course of multiple sclerosis (MS) make diagnosis and prognosis difficult. This has resulted in an unmet need for clinically validated, quantitative serum-based tests that can accurately monitor MS disease activity and progression. A team from the Brigham and Women’s Hospital at Harvard Medical School have reported the outcome of a study to clinically validate a multi-protein panel for monitoring disease activity in MS patients. The Multiple Sclerosis Disease Activity (MSDA) panel, based on Olink® Proximity Extension Assay (PEA) technology and developed by Octave Bioscience has previously gone through a technical validation (Qureshi et al., 2023, Proteomics Clinical Applications). In the present study, the MSDA panel was validated from the clinical perspective using 614 serum samples from two independent sources (SUMMIT & RMMSC) by evaluating the associations of protein levels with the overall DA score and four disease pathway scores, based on a composite of radiographic and clinical evidence.
Outcome
The protein model was trained based on presence/absence of gadolinium-positive (Gd+) lesions (indicators of disease severity) and was also strongly associated with emergence of new lesions, and overall disease activity (radiographic and clinical evidence). Patients with a high MSDA score were ~21x more likely to have 2 or more Gd+ lesions than those with a low/moderate DA score, and ~4.5x more likely to have 1 or more Gd+ lesions compared to patients with a moderate/high MSDA score. The panel outperformed the top-performing single-protein model (neurofilament light) – for example when comparing active vs stable disease, the MSDA model had an AUC=0.768 compared to 0.683 for Nfl alone. The authors concluded that the MSDA Test was clinically validated and can serve as a quantitative tool to enhance the care of MS patients.
