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Boswellic acids immunomodulate T cell populations in relapsing-remitting multiple sclerosis in the SABA phase IIa clinical trial

: Stürner, K.H.; Stellmann, J.-P.; Dörr, J.-M.; Paul, F.; Keminer, O.; Vaas, L.; Pless, O.; Martin, R.; Heesen, C.

Multiple sclerosis 22 (2016), Nr.3, Supplement, S.290-291
ISSN: 1352-4585
ISSN: 1477-0970
European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS Congress) <32, 2016, London>
Bundesministerium für Bildung und Forschung BMBF
Fraunhofer IME ()

Background: Boswellic Acids (BAs), the main biologically active compound of frankincense (Boswellia ssp.), are orally available and have exhibited a safe and favourable side effect profile for the treatment of relapsing-remitting Multiple Sclerosis (RR-MS) in an open-label, two-center, baseline-to-treatment phase IIa trial. Effects on the primary MRI outcome and secondary clinical outcome parameters strongly suggest a positive influence on disease activity in RR-MS patients. BAs are known to exhibit anti-inflammatory activities, however, their immunological effect/s in RR-MS patients are not fully understood.
Methods: In parallel to the phase IIa study with a standardized frankincense extract (produced by Alpinia Laudanum, Switzerland, and containing BAs as active ingredient) we performed an immunological substudy in n = 28 BA-treated RR-MS patients, who completed the study. Multicolour flow cytometric analysis was performed longitudinally ex vivo in n = 26 patients at three time points before, during early and during late treatment, respectively. Cytokine levels for interleukin(IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, tumor necrosis factor-alpha, interferon-gamma and transforming growth factor-beta in serum were measured at the same time points in n = 28 patients by highly sensitive single or multiplex analysis (MesoScale; Singulex) after all patients had completed the study.
Results: We observed distinct alterations in CD3+ T cell subpopulations in our BA-treated patient cohort: While in the CD4+ T cell subset CTLA-4 expression and the percentage of CD4+CD25high Foxp3+ T cells increased significantly during treatment (p < 0.01), we found a significant decrease in the percentage of IL17-producing CD8+T cells coinciding with an increase in IL10-producing CD8+ T cells (p < 0.01). The analysis of other leucocyte and lymphocyte subpopulations, i.e. monocytes, B cells, natural killer cells and dendritic cells showed no alterations before and after BA-treatment. White blood cell counts and lymphocyte counts in general remained unaltered throughout the whole study. In regard to cytokine levels in serum, we observed significant decreases in IL-17A, GM-CSF and IL-2 during BA-treatment (p < 0.05).
Conclusions: Treatment with boswellic acids in a phase IIa clinical trial leads to immunomodulatory effects on T cell subsets consistent with the inhibition of inflammatory disease activity as shown by MRI and clinical outcomes.