SPINCOMS Biomarker Study

Using machine learning, the investigators have developed from SOMAScan:

A molecular diagnostic test that differentiates MS from other inflammatory and non-inflammatory central nervous system (CNS) diseases (area under receiver-operator characteristic curve-AUROC of 0.98);
A molecular test that differentiates relapsing-remitting MS from progressive MS variants (AUROC of 0.91); and
A molecular test that predicts future rates of disability progression, concordance coefficient of 0.425 (p<0.001).

Because these results are derived from a single research center (NIAID/NDS), it is imperative to determine their performance in real clinical practice settings as a necessary step for their potential regulatory approval.

Consequently, this application has 2 specific aims:

AIM 1. To independently validate afore-mentioned CSF-biomarker-based tests for their clinical value within the multicenter Spinal fluid Consortium for MS (SPINCOMS). In Aim 1, each of the 3 defined tests will be validated in 100 new SPINCOMS patients. To validate the prognostic test, 100 MS patients with CSF collected at least 3 years ago will be evaluated at follow-up examination with standardized clinical outcomes. CSF will be analyzed blinded using pre-defined statistical models.

AIM 2. To explore whether collected CSF-biomarkers point towards pathogenic heterogeneity that may predict patient-specific efficacy for different disease-modifying treatments (DMTs) or identify pathogenic mechanisms not targeted by current DMTs. In Aim 2, clustering analysis will assess pathogenic heterogeneity and explore potential predictors of response to therapy.