Magnetic Resonance Imaging (MRI) Characterization of the Therapeutic Effect of Glatiramer Acetate in Different Models of Experimental Autoimmune Encephalomyelitis (EAE) (P05.109)

Abstract

Objective: To study the different pathological manifestations in chronic versus relapsing-remitting experimental autoimmune encephalomyelitis (EAE) and the in situ therapeutic effect of glatiramer acetate (GA, Copaxoneâ) using advanced magnetic resonance imaging (MRI) parameters. Background The respective roles of inflammatory and neurodegenerative processes in multiple sclerosis and its EAE models are controversial. The immunomodulator GA alleviates MS/EAE pathological inflammation and induces neuroprotective repair processes within the CNS. MRI is an essential noninvasive tool for in vivo evaluation of MS therapies. Design/Methods: Mice inflicted with chronic MOG or relapsing-remitting PLP peptide-induced EAE were treated with GA (7 daily injections) starting after disease induction (prevention) or after clinical symptoms development (suppression). Brain MRI measurements were performed at several time points along disease progression. MRI protocols included transverse T2, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI), analyzed both by whole brain histograms and by voxel based analysis. Results: Brains of EAE mice of both models revealed increased T2-values with associated enlargement of ventricle size indicating substantial CNS inflammation. Ventricle swelling was characteristic to the PLP-induced model in which 5-fold elevation of ventricle size was detected. Decreased MTR values and increased apparent diffusion coefficient (ADC) were observed mainly in MOG-induced mice indicative of macromolecular loss and structural CNS damage involvement in the chronic disease. GA applied by both prevention and suppression regimens affected all the MRI pathological manifestations, resulting in significant reduction of T2 values and ventricle volume, elevated MTR and decreased ADC in comparison to sham-treated mice. Furthermore, following GA treatment, histogram peaks of all MRI parameters were statistically not different from naive controls. Conclusions: Inflammatory manifestations are involved in both EAE models, whereas macromolecular loss and structural CNS damage are more prominent in chronic EAE. GA improves MRI parameters: T2-relaxation, ventricle swelling, MTR and ADC indicating its in situ anti-inflammatory and repair consequences. Supported by: Teva. Disclosure: Dr. Aharoni has nothing to disclose. Dr. Sason has nothing to disclose. Dr. Sela has received royalty payments from Teva Neuroscience. Dr. Sela holds stock and/or stock options in Teva Neuroscience. Dr. Sela has received research support from Teva Neuroscience. Dr. Arnon has received royalty payments from Teva Neuroscience. Dr. Arnon has received research support from Teva Neuroscience.