Commentary

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Potential Role of Glial Fibrillary Acidic Protein in Progressive Multiple Sclerosis: Robert J. Fox, MD

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The vice-chair for research at Cleveland Clinic’s Neurological Institute provided commentary on the expanded research of GFAP in multiple sclerosis and whether certain biomarkers may predict treatment response. [WATCH TIME: 8]

WATCH TIME: 8 minutes

"The CSF (cerebrospinal fluid) measures of those molecules [neurofilament light, GFAP] did not correlate with clinical or imaging measures of the tissue destruction. That was a little surprising because a lot of people think that CSF is a more direct and relevant compartment to measure these molecules."

In 2018, data from the phase 2 SPRINT-MS trial (NCT01982942) published in the New England Journal of Medicine highlighted the effects of ibudilast in patients with progressive multiple sclerosis (MS). Over a 96-week treatment period, findings showed that treatment with the agent was associated with slower progression of brain atrophy than placebo, with approximately 2.5 ml less brain-tissue loss observed.

Years later, at MSMilan 2023, the joint ECTRIMS-ACTRIMS meeting, held October 11-13, 2023, in Milan, Italy, an analysis of the study evaluated whether glial fibrillary acidic protein (GFAP) and Contactin-1, 2 prominent central nervous system biomarkers, could be used to evaluate treatment response in progressive MS. Over the 96-week timeframe, the estimated change in serum GFAP was 2.88% increased/year in placebo and 2.13% increase/year in ibudilast (P = .68). Corresponding changes in cerebrospinal fluid GFAP were 2.69% decrease/year in placebo and 0.29% decrease/year with ibudilast (P = .62). Additionally, change over time in Contactin-1 was no different between treatment groups in serum (P = .32) and CSF (P = .43).

Led by Robert J. Fox, MD, neurologist, Mellen Center for Multiple Sclerosis, and vice-chair for research, Neurological Institute, Cleveland Clinic, the study did not support either GFAP or Contactin-1 as treatment response biomarkers. Following the meeting, Fox sat down with NeurologyLive® to give his thoughts on the data and how it adds to the growing literature of GFAP in MS. He spoke on the role of critical biomarkers in assessing treatment response and the potential directions the clinical community needs to take.

Click here for more coverage of MSMilan 2023.

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