Contributions
Abstract: EP1677
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Introduction: Dimethylfumarate (DMF) is a therapeutic for multiple sclerosis (MS). The exact mechanism of action is still unknown, however, DMF is thought to promote Th2 polarization of T-cells.
Objectives: The objective of this study was to determine the efficacy of DMF therapy in two different types of focal EAE models.
Aims: Longitudinal positron emission tomography (PET) imaging was performed using the translocator protein (18 kDa, TSPO) -tracer [18F]GE-180 to detect the progression of neuroinflammation during therapy.
Methods: Delayed type hypersensitivity (DTH) and a myelin oligodendrocyte glycoprotein (MOG) EAE rat models were induced by peripheral activation of the immune system and by injecting antigens in a stereotaxic operation. The rats were treated orally twice daily before the lesion formation (starting on day 0 after lesion induction) either with H2O (control group n = 4) or with DMF (15mg/kg) diluted in 0.08% methocel and water (n = 4). The animals were imaged with [18F]GE-180 on days 0, 7, 14, and 33 (DTH), or on day 14, 33 or 56 (MOG), and the binding potential (BPND) was calculated.
Results: DMF reduced the BPND in the treated animals in the DTH-model when compared to the control animals at day 7 (two-tailed unpaired t-test, p = 0.031) and at day 33 (p = 0.040), but not at day 14 (p = 0.66). In the MOG-model the treatment showed a trend towards decreased inflammation in the treated animals at day 14 (p = 0.088). The analysis of histological events is still on-going.
Conclusions: DMF reduces neuroinflammation in the DTH-model after 7 and 33 days of treatment, but at day 14 it did not seem to inhibit lesion formation. In the MOG-model treatment effect was not detected at day 14 or day 33. The research leading to these results has received funding from the European Union´s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° HEALTH-F2-2011-278850 (INMiND). The study was supported by BiogenIdec, GE Healthcare and the Swedish Cultural Foundation in Finland.
Disclosure: Vainio S K: nothing to disclose
Dickens A M: nothing to disclose
Lopez-Picon F R: nothing to disclose
Eskola O: nothing to disclose
Solin O: nothing to disclose
Rinne J: Dr. Rinne serves as a neurology consultant for CRST Oy (Clinical Research Services Turku).
Airas L: Dr. Airas has received honoraria from Biogen, F. Hoffmann-La Roche Ltd, Genzyme, Merck Serono and Teva, and institutional research grant support from Biogen, Genzyme, Merck Serono and Novartis.
Anthony D C: nothing to disclose
Haaparanta-Solin M: nothing to disclose
Abstract: EP1677
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Introduction: Dimethylfumarate (DMF) is a therapeutic for multiple sclerosis (MS). The exact mechanism of action is still unknown, however, DMF is thought to promote Th2 polarization of T-cells.
Objectives: The objective of this study was to determine the efficacy of DMF therapy in two different types of focal EAE models.
Aims: Longitudinal positron emission tomography (PET) imaging was performed using the translocator protein (18 kDa, TSPO) -tracer [18F]GE-180 to detect the progression of neuroinflammation during therapy.
Methods: Delayed type hypersensitivity (DTH) and a myelin oligodendrocyte glycoprotein (MOG) EAE rat models were induced by peripheral activation of the immune system and by injecting antigens in a stereotaxic operation. The rats were treated orally twice daily before the lesion formation (starting on day 0 after lesion induction) either with H2O (control group n = 4) or with DMF (15mg/kg) diluted in 0.08% methocel and water (n = 4). The animals were imaged with [18F]GE-180 on days 0, 7, 14, and 33 (DTH), or on day 14, 33 or 56 (MOG), and the binding potential (BPND) was calculated.
Results: DMF reduced the BPND in the treated animals in the DTH-model when compared to the control animals at day 7 (two-tailed unpaired t-test, p = 0.031) and at day 33 (p = 0.040), but not at day 14 (p = 0.66). In the MOG-model the treatment showed a trend towards decreased inflammation in the treated animals at day 14 (p = 0.088). The analysis of histological events is still on-going.
Conclusions: DMF reduces neuroinflammation in the DTH-model after 7 and 33 days of treatment, but at day 14 it did not seem to inhibit lesion formation. In the MOG-model treatment effect was not detected at day 14 or day 33. The research leading to these results has received funding from the European Union´s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° HEALTH-F2-2011-278850 (INMiND). The study was supported by BiogenIdec, GE Healthcare and the Swedish Cultural Foundation in Finland.
Disclosure: Vainio S K: nothing to disclose
Dickens A M: nothing to disclose
Lopez-Picon F R: nothing to disclose
Eskola O: nothing to disclose
Solin O: nothing to disclose
Rinne J: Dr. Rinne serves as a neurology consultant for CRST Oy (Clinical Research Services Turku).
Airas L: Dr. Airas has received honoraria from Biogen, F. Hoffmann-La Roche Ltd, Genzyme, Merck Serono and Teva, and institutional research grant support from Biogen, Genzyme, Merck Serono and Novartis.
Anthony D C: nothing to disclose
Haaparanta-Solin M: nothing to disclose