Contributions
Abstract: P1240
Type: Poster
Abstract Category: Therapy - disease modifying - 32 Others
Background: Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that regulate lipid metabolism and immune processes. CD36 receptor is an innate immune receptor upregulated by PPAR γ. PPARs have been implicated in multiple sclerosis (MS) and suggested as potential targets for its treatment. The mechanisms underlying the anti-inflammatory and neuroprotective effects of Fingolimod in MS are not fully understood. Fingolimod acts as a sphigosine-1-phosphate mimetic, suggesting a link between its immunomodulatory effects and lipid metabolism. We hypothesized that PPAR and CD36-mediated processes could be involved in the mechanisms of action of Fingolimod therapy.
Objective: The aim of this work was to investigate gene expression of PPARα, PPARβ/δ, PPARγ and CD36 in blood leukocytes and associated plasma lipid profile in MS patients treated with Fingolimod.
Methods: 12 women with the diagnosis of relapsing-remitting MS (age 39 SD 7.5) and 10 (SD 8.5) years of disease duration were recruited from two MS clinical centres in the Lisbon area. All patients were scheduled to start Fingolimod and switch to this treatment because poor response or adverse effects with previous immunomodulatory agents. Plasma lipid profile was analysed and PPAR and CD36 mRNA expression was measured by quantitative RT-PCR in total blood leukocytes, before and 6 months after the initiation of Fingolimod treatment. The Student´s t-test was used for parametric and the Wilcoxon rank sum for non-parametric analysis.
Results: Under Fingolimod therapy, PPARγ gene expression increased by 90% (p=0.013) and CD36 increased about 70% (p=0.017). In contrast, PPARα and PPARβ/δ were unchanged. HDL cholesterol level increased (p=0.015) and the total cholesterol/HDL ratio (p=0.041) and LDL cholesterol level (p=0.005) decreased with treatment.
Conclusions: These data suggest an involvement of PPAR-mediated processes and lipid metabolism in the mechanism of action of Fingolimod.
Disclosure: This work was supported by a grant from Novartis in Portugal and statistical assistance from Keypoint, Scientific Consulting Lda, Miraflores, Portugal.
Abstract: P1240
Type: Poster
Abstract Category: Therapy - disease modifying - 32 Others
Background: Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that regulate lipid metabolism and immune processes. CD36 receptor is an innate immune receptor upregulated by PPAR γ. PPARs have been implicated in multiple sclerosis (MS) and suggested as potential targets for its treatment. The mechanisms underlying the anti-inflammatory and neuroprotective effects of Fingolimod in MS are not fully understood. Fingolimod acts as a sphigosine-1-phosphate mimetic, suggesting a link between its immunomodulatory effects and lipid metabolism. We hypothesized that PPAR and CD36-mediated processes could be involved in the mechanisms of action of Fingolimod therapy.
Objective: The aim of this work was to investigate gene expression of PPARα, PPARβ/δ, PPARγ and CD36 in blood leukocytes and associated plasma lipid profile in MS patients treated with Fingolimod.
Methods: 12 women with the diagnosis of relapsing-remitting MS (age 39 SD 7.5) and 10 (SD 8.5) years of disease duration were recruited from two MS clinical centres in the Lisbon area. All patients were scheduled to start Fingolimod and switch to this treatment because poor response or adverse effects with previous immunomodulatory agents. Plasma lipid profile was analysed and PPAR and CD36 mRNA expression was measured by quantitative RT-PCR in total blood leukocytes, before and 6 months after the initiation of Fingolimod treatment. The Student´s t-test was used for parametric and the Wilcoxon rank sum for non-parametric analysis.
Results: Under Fingolimod therapy, PPARγ gene expression increased by 90% (p=0.013) and CD36 increased about 70% (p=0.017). In contrast, PPARα and PPARβ/δ were unchanged. HDL cholesterol level increased (p=0.015) and the total cholesterol/HDL ratio (p=0.041) and LDL cholesterol level (p=0.005) decreased with treatment.
Conclusions: These data suggest an involvement of PPAR-mediated processes and lipid metabolism in the mechanism of action of Fingolimod.
Disclosure: This work was supported by a grant from Novartis in Portugal and statistical assistance from Keypoint, Scientific Consulting Lda, Miraflores, Portugal.