GFAP protein may help predict MS severity, response to treatment
Findings support use of blood levels of GFAP as biomarker
Blood levels of a protein called GFAP, which reflects the activation and damage to support cells in the brain and spinal cord, may help predict disease severity and the response to treatment with relapsing forms of multiple sclerosis (MS), according to a new analysis of clinical trial data.
“This exploratory, post hoc analysis … adds to the current body of knowledge that GFAP is an informative biomarker of relapse-independent baseline MS disease severity and a predictor of response to treatment in participants with [relapsing MS],” the study’s researchers wrote. The study, “Glial Fibrillary Acidic Protein as a Marker of Disease in Relapsing Multiple Sclerosis: Post Hoc Analysis of Phase 3 Ozanimod Trials,” was published in the European Journal of Neurology.
GFAP, or glial fibrillary acidic protein, is a molecule that provides structural support to astrocytes, star-shaped brain cells that help maintain the health of nerve cells. When astrocytes become activated in response to tissue damage or inflammation, they produce more GFAP. If these cells are also injured or stressed, GFAP can leak into the bloodstream. Higher levels of GFAP have been linked to greater disability and disease activity in MS.
GFAP as MS biomarker
To explore GFAP’s potential as a biomarker, researchers analyzed data from SUNBEAM (NCT02294058) and RADIANCE (NCT02047734), two large Phase 3 clinical trials. The studies collectively enrolled 2,659 adults with relapsing forms of MS and randomly assigned them to a daily dose of oral MS therapy Zeposia (ozanimod) or a weekly injection of Avonex (interferon beta-1a).
Blood samples collected at the start of the trials were used to measure GFAP levels in most participants (77.3%). The study was funded by Bristol Myers Squibb, which markets Zeposia.
In a first analysis, the researchers assessed if starting, or baseline, GFAP levels correlated with any other baseline factors, such as demographics or disease characteristics. Results showed GFAP levels were associated with sex and baseline body mass index, which is a measure that uses weight and height to determine a person’s body fat. Those with higher baseline GFAP levels also had significantly higher levels of neurofilament light chain (NfL), a biomarker of nerve cell damage, more lesions, and higher disability scores at the trials’ start.
In a subsequent analysis, baseline GFAP levels also showed significant associations with clinical outcomes while on treatment. In particular, higher levels were an independent predictor of relapses in the first year of treatment.
Other clinical outcomes, such as number of lesions, brain volume, and disability scores at one and two years also showed some associations, but they lost significance when other baseline factors were considered.
The findings “provide some support for the use of [blood] GFAP as a biomarker for disease severity and response to treatment in participants with [relapsing MS],” the researchers wrote.
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