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. 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.
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. 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).
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.
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.
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.
Talks and Interviews[edit | edit source]
- 2011, 6th Invest in ME International ME Conference 2011 - B-cell Depletion Therapy Using Rituximab in ME/CFS - Part II
- 2012, 7th Invest in ME International ME Conference 2011 - B-cell Depletion Therapy Using Rituximab in ME/CFS - Part II
- 2013, 8th Invest in ME International ME Conference 2012 - B-cell Depletion Therapy Using Rituximab in ME/CFS - Part II
- 2015, The Naked Scientists Podcast -"Is ME an autoimmune disease?"
- 2016, 12th International IACFS/ME Biennial Clinical and Research Conference, Emerging Science and Clinical Care, Plenary Speaker
- 20 Oct 2016, Ongoing Clinical Research in the ME/CFS Research Group of the RituxME and CycloME studies"
- 26 Jan 2017, BBC Look East: Research in Norwich could offer ME/CFS breakthrough
- Jan 2017, Public talk in Norwich on ME/CFS biomedical research hosted by Institute Food Research and Invest in ME Research
- Jan 2017, TV 2 Nyhetskanalen interview about ME/CFS and Dr. Øystein Fluge's latest research (with English subtitles)
Notable ME/CFS Studies[edit | edit source]
- 2011, Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study - (Full text)
- 2015, B-lymphocyte depletion in myalgic encephalopathy/chronic fatigue syndrome. An open-label phase II study with rituximab maintenance treatment - (Full text)
- 2016, Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome - (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.
- 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."
- 2018, Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - (Full text)
- 2018, Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome - (Abstract)
- 2019, B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial
- 2019, Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome - (Full text)
See also[edit | edit source]
Learn more[edit | edit source]
References[edit | edit source]
- 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
- 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
- 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
- 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
- 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
- Günther, Oliver P.; Gardy, Jennifer L.; Stafford, Phillip; Fluge, Øystein; Mella, Olav; Tang, Patrick; Miller, Ruth R.; Parker, Shoshana M.; Johnston, Stephen A. (Oct 8, 2018). "Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)". Molecular Neurobiology. doi:10.1007/s12035-018-1354-8. ISSN 0893-7648.
- Schjøtt, Jan; Vries, Annick de; Mella, Olav; Sørland, Kari; Risa, Kristin; Alme, Kine; Fluge, Øystein; Rekeland, Ingrid G. (Nov 28, 2018). "Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome". Clinical Therapeutics. 0 (0). doi:10.1016/j.clinthera.2018.10.019. ISSN 1879-114X. PMID 30502905.
- Fluge, Øystein; Rekeland, Ingrid G.; Lien, Katarina; Thürmer, Hanne; Borchgrevink, Pette C.; Schäfer, Christoph; Sørland, Kari; Aßmus, Jörg; Ktoridou-Valen, Irini; Mella, Olav (Apr 2, 2019). "B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial". Annals of Internal Medicine. doi:10.7326/M18-1451. ISSN 0003-4819.
- Giannoccaro, Maria Pia; Cossins, Judith; Sørland, Kari; Fluge, Øystein; Vincent, Angela (May 2019). "Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome". Clinical Therapeutics. 41 (5): 836–847. doi:10.1016/j.clinthera.2019.04.001.
Myalgic encephalomyelitis or chronic fatigue syndrome