Abstract Details

Title Gene Expression Biomarkers for Glatiramer Acetate Treatment Response in Relapsing-Remitting Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 142

Objective

Background BACKGROUND: GA is known to be effective for the treatment of RRMS, in reducing the number of relapses and suppressing disease progression. However, currently, there is no tool for predicting treatment efficacy - either good or poor in individual patients.

Design/Methods DESIGN/METHODS: We used 37 HG-U133A2 (Affymetrix) gene-expression microarrays, to analyze peripheral blood samples taken prior treatment initiation with GA (n=37, 25 females, age 38.6±1.7 years, disease duration 6.4±1.2 years, expanded disability status scale (EDSS) 2.1±0.2). Good treatment response at 2 years of treatment was defined as reduction by at least 1 relapse compared with the 2 years rate prior to treatment combined with annual increase of up to 0.5 in the EDSS score. Statistical comparison of the baseline expression of differentiating genes between responders and non-responders patients was performed to identify potential markers for treatment response.

Results RESULTS: Good clinical outcome was observed in 25/37 (67%) GA treated patients. A signature of 762 gene-transcripts differentiated between good and poor responders at baseline, significantly enriched with genes related to apoptosis (P=5.27E-05) and inflammation (P=6.28E-05). A 3-gene classifier including ACTR5, WDR45, and PPP1R13B, all known to be related to apoptosis, showed robust discrimination rate for treatment response (93.8%) with 96% (24/25) sensitivity, and 100% (12/12) specificity. These genes expressed individual prediction ability demonstrated by large area under the curve (AUC) (range 0.865-0.902), high sensitivity (range 68-100%) and high specificity (range 72-100%).

Conclusions CONCLUSIONS: Our findings demonstrate that baseline gene expression pattern of elevated apoptotic related genes signify good response for GA treatment. Three genes associated with apoptosis (ACTR5, WDR45, PPP1R13B) showed high prediction ability for treatment outcome and can serve as potential biomarkers.

Authors/Disclosures
Saar Anis, MD (Cleveland Clinic) PRESENTER	Dr. Anis has nothing to disclose.
	No disclosure on file
Erez Hanael	No disclosure on file
Michael Gurevich (Sheba Medical Center)	No disclosure on file
Anat Achiron, MD, PhD, FAAN (Sheba Medical Center, Tel-Hashomer)	Dr. Achiron has nothing to disclose.
	No disclosure on file

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