Abstract: Phosphorylated SIRT1 As a Biomarker of Relapse and Response to Treatment with Glatiramer Acetate in Multiple Sclerosis (2018 Annual Meeting of the Consortium of Multiple Sclerosis Centers)

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Phosphorylated SIRT1 As a Biomarker of Relapse and Response to Treatment with Glatiramer Acetate in Multiple Sclerosis

Thursday, May 31, 2018

Exhibit Hall A (Nashville Music City Center)

Jonathan Ciriello, B.S. , Department of Neurology, University of Maryland School of Medicine, Baltimore, MD

Alexandru Tatomir, M.D. , Department of Neurology, University of Maryland School of Medicine, Baltimore, MD

Daniel Hewes, B.S. , Department of Neurology, University of Maryland School of Medicine, Baltimore, MD

Vinh Nguyen, D.D.S. , Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, MD

Walter Royal III, M.D. , Veterans Administration Multiple Sclerosis Center of Excellence, Baltimore, MD

Violeta Rus, M.D., Ph.D. , Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, MD

Horea Rus, M.D., Ph.D. , Veterans Administration Multiple Sclerosis Center of Excellence, Baltimore, MD

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Background:

SIRT1 is a class III histone deacetylase that acts as an NAD⁺-dependent histone and protein deacetylase. SIRT1 is activated by phosphorylation at multiple residues and can act to modulate cellular transcription and survival. We have previously shown that SIRT1 mRNA in peripheral blood mononuclear cells (PBMC) is significantly lower in multiple sclerosis (MS) patients during clinical relapse as compared to clinically stable patients.

Objectives:

Investigate the role of phosphorylated SIRT1 (p-SIRT1) and its downstream target, trimethylation of histone 3 lysine 9 (H3K9me3), as possible biomarkers for relapse and response to treatment with glatiramer acetate (GA) in patients with relapsing remitting MS (RRMS).

Methods:

Over two years, a cohort of 16 patients with RRMS were treated with GA, monitored for clinical relapse, and followed clinically using the Expanded Disability Status Scale (EDSS). Blood samples were taken from patients at study enrollment and at 3, 6, and 12 months after initiating GA treatment. Protein expression of p-SIRT1, SIRT1, H3K9me3, and β-actin was measured in patients’ isolated PBMCs by western blot analysis.

Results:

p-SIRT1 levels were significantly decreased in MS patients experiencing clinical relapse compared to clinically stable patients (p = 0.0021) and in non-responders to GA treatment compared to responders (p = 0.0306). H3K9me3 levels were significantly decreased in MS patients experiencing clinical relapse compared to clinically stable patients (p = 0.0007). p-SIRT1 levels inversely correlated with the EDSS score at lower disability levels (r = -0.391, p = 0.0115). Receiver operating characteristic (ROC) analysis suggests that p-SIRT1 (AUC = 0.701) and H3K9me3 (AUC = 0.766) may be possible biomarkers for detecting relapse in MS and that H3K9me3 (AUC = 0.707) is a potential biomarker for detecting response to treatment with GA.

Conclusions:

Our data suggest that p-SIRT1 and H3K9me3 are potential biomarkers to detect relapse in patients with MS and that H3K9me is a potential biomarker to detect response to treatment with GA.

NB01 Phosphorylated SIRT1 As a Biomarker of Relapse and Response to Treatment with Glatiramer Acetate in Multiple Sclerosis

NB01
Phosphorylated SIRT1 As a Biomarker of Relapse and Response to Treatment with Glatiramer Acetate in Multiple Sclerosis