Øystein Fluge

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Source:InvestinME

Øystein Fluge, MD, is the Senior Consultant supervising the ME/CFS research group at the Department of Oncology and Medical Physics at the University of Bergen, Haukeland University Hospital, Bergen, Norway.[1] He works with Professor Olav Mella in the Norwegian Rituximab and cyclophosphamide trials employing the depletion of B cell lymphocytes in ME/CFS patients.

Dr. Fluge is a member of the Working Group which offers their expertise and resources to the ME/CFS Collaborative Research Center at Stanford University.[2]

Rituximab work in ME/CFS[edit | edit source]

Øystein Fluge's and Olav Mella's discovery was found by accident, in that three ME/CFS patients who had B-cell lymphoma improved remarkably following treatment with Rituximab. Not only had their lymphomas improved, but all symptoms of their ME/CFS diminished with the treatment. The positive responses were delayed for up to 6-12 weeks, despite their B cells being eliminated by the drug in 2 weeks. Since that accidental discovery, a larger study has been undertaken. Initial reports were promising in that there is a positive response in 67% of the patients receiving Rituximab vs a 13% improvement in the placebo group. After the effects wore off, there was a decline in the numbers who responded to the second and subsequent infusions.[3] The clinical trial, named RituxME, was a multicenter, phase III study. It was randomized, double-blind and placebo controlled, with 152 participants, of which half will receive treatments with rituximab and the other half will be treated with placebo (saline).[4]

On Nov 21, 2017, Drs. Øystein Fluge and Olav Mella announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The Drs. will publish a paper next year with the specifics of the failed trial.[5]

The discovery of ME/CFS patients responding positively to an autoimmunity drug has radically changed how many have viewed ME/CFS, to the point that Bjørn Guldvog, the Deputy Director General of Norwegian Directorate of Health, has apologized for the way in which ME patients in Norway have been treated: "I think that we have not cared for people with ME to a great enough extent. I think it is correct to say that we have not established proper health care services for these people, and I regret that." The European ME Alliance believes that such a public apology from a governmental health agency has never occurred before.[6]

In 2015, a second clinical trial for ME/CFS by the same group headed by Fluge and Mella, was started using the chemotherapy drug, cyclophosphamide. Called CycloME part A​, this study will involve 40 patients with moderate and severe ME/CFS and will be ongoing until January 2017. If the results indicate a clinically relevant response, i.e., an improvement in symptoms, in a minimum of 40% of the patients, the trial will move into CycloME part B and may be extended to include patients with very severe ME.[7]

Talks and Interviews[edit | edit source]

Notable ME/CFS Studies[edit | edit source]

  • 2016, Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome[8] (Full Text)
  • 2016, Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome.[9]
  • 2016, Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome. The study abstract states: "The association of autoantibodies with immune markers suggests that they activate B and T cells expressing β adrenergic and M acetylcholine receptors. Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS."[10]
  • 2015, B-lymphocyte depletion in myalgic encephalopathy/chronic fatigue syndrome. An open-label phase II study with rituximab maintenance treatment[11] (Full Text)
  • 2011, Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study[12] (Full Text)

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. http://www.helse-bergen.no/en/OmOss/Avdelinger/kreft/forsking-fagutvikling/Sider/Forsking-p%C3%A5-ME.aspx
  2. https://bos.etapestry.com/prod/viewEmailAsPage.do?erRef=773.0.423082047&databaseId=OMF&mailingId=34274682&jobRef=773.0.506425459&key=b6b9237b3ebd1e462a5d11dbc5c4dae&personaRef=773.0.423082048&memberId=1348639685
  3. http://www.investinme.eu/IIMEC7.shtml
  4. http://www.helse-bergen.no/en/OmOss/Avdelinger/kreft/forsking-fagutvikling/Sider/RituxME.aspx
  5. http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/
  6. http://www.euro-me.org/news-Q42011-003.htm
  7. http://www.helse-bergen.no/en/OmOss/Avdelinger/kreft/forsking-fagutvikling/Sider/CycloME.aspx
  8. Fluge, Øystein; Mella, Olav; Bruland, Ove; Risa, Kristin; Dyrstad, Sissel E.; Alme, Kine; Rekeland, Ingrid G.; Sapkota, Dipak; Røsland, Gro V.; Fosså, Alexander; Ktoridou-Valen, Irini; Lunde, Sigrid; Sørland, Kari; Lien, Katarina; Herder, Ingrid; Thürmer, Hanne; Gotaas, Merete E.; Baranowska, Katarzyna A.; Bohnen, Louis M.L.J.; Schäfer, Christoph; McCann, Adrian; Sommerfelt, Kristian; Helgeland, Lars; Ueland, Per M.; Dahl, Olav; Tronstad, Karl J. (2016), "Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome", JCI Insight, 1 (21), doi:10.1172/jci.insight.89376
  9. Lunde S, Kristoffersen EK, Sapkota D, Risa K, Dahl O, Bruland O, et al. (2016) Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome. PLoS ONE 11(8): e0161226. doi:10.1371/journal.pone.0161226
  10. Loebel, M; Grabowski, P; Heidecke, H; Bauer, S; Hanitsch, LG; Wittke, K; Meisel, C; Reinke, P; Volk, H; Fluge, Ø; Mella, O; Scheibenbogen, C (2016), "Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome", Brain, behavior, and immunity, 52: 32-39, doi:10.1016/j.bbi.2015.09.013
  11. Fluge, Ø ; Risa, K ; Lunde, S; Alme, K ; Rekeland, IG; Sapkota, D; Kristoffersen, EK; Sørland, K; Bruland, O; Dahl, O; Mella, O. 2015. B-lymphocyte depletion in myalgic encephalopathy/chronic fatigue syndrome. An open-label phase II study with rituximab maintenance treatment. PLoS One,10(7):e0129898. doi: 10.1371/journal.pone.0129898
  12. Fluge, Øystein; Bruland, Ove; Risa, Kristin; Storstein, Anette; Kristoffersen, Einar Klæboe; Sapkota, Dipak; Næss, Halvor; Dahl, Olav; Nyland, Harald Inge; Mella, Olav (2011), "Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.", PLoS One, 6 (10): e26358, doi:10.1371/journal.pone.0026358