Øystein Fluge

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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 worked with Professor Olav Mella in the Norwegian Rituximab and cyclophosphamide trials employing the depletion of B cell lymphocytes in ME/CFS patients.[2]

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.[3]

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.[4] 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).[5]

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.[6]

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.[7]

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.[8] 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.[9]

Talks and interviews[edit | edit source]

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[10] - (Full text)
  • 2015, B-lymphocyte depletion in myalgic encephalopathy/chronic fatigue syndrome. An open-label phase II study with rituximab maintenance treatment[11] - (Full text)
  • 2016, Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome[12] - (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.[13]
  • 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."[14]
  • 2018, Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)[15] - (Full text)
  • 2018, Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome[16] - (Abstract)
  • 2019, B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial[17]
  • 2019, Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome[18] - (Full text)

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. "Øystein Fluge, MD, PhD & Olav Mella, MD, PhD". Open Medicine Foundation. Retrieved Oct 10, 2019. 
  2. "ME/CFS research". Helse Bergen (in norsk). Retrieved Oct 10, 2019. 
  3. "OMF grants $1.2M to Ramp Up Collaborative Research Center at Stanford University". bos.etapestry.com. Retrieved Sep 12, 2019. 
  4. "Invest in ME Research - International ME Conferences and Colloquiums Home Page". investinme.org. Retrieved Sep 12, 2019. 
  5. "RituxME". Helse Bergen. Retrieved Sep 10, 2019. 
  6. "Norwegian Rituximab Chronic Fatigue Syndrome (ME/CFS) Trial Fails". Simmaron Research. Nov 26, 2017. Retrieved Sep 12, 2019. 
  7. "European ME Alliance - Norway's Directorate of Health Apologises to ME Patients for Poor Treatment". www.euro-me.org. Retrieved Sep 12, 2019. 
  8. "CycloME part A". Helse Bergen (in norsk). Retrieved Oct 10, 2019. 
  9. "CycloME part B". Helse Bergen (in norsk). Retrieved Oct 10, 2019. 
  10. 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 
  11. Fluge, Øystein; Risa, Kristin; Lunde, Sigrid; Alme, Kine; Rekeland, Ingrid Gurvin; Sapkota, Dipak; Kristoffersen, Einar Kleboe; Sørland, Kari; Bruland, Ove (Jul 1, 2015). van der Feltz-Cornelis, Christina, ed. "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. ISSN 1932-6203. PMC 4488509Freely accessible. PMID 26132314. 
  12. 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 
  13. Lunde, Sigrid; Kristoffersen, Einar K.; Sapkota, Dipak; Risa, Kristin; Dahl, Olav; Bruland, Ove; Mella, Olav; Fluge, Øystein (Aug 18, 2016). Cordero, Mario D., ed. "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. ISSN 1932-6203. 
  14. 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 
  15. 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. 
  16. 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. 
  17. 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. 
  18. 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, often used when both illnesses are considered the same.

Last phase of clinical trials before a drug can be approved for public use.[1]

Myalgic encephalomyelitis or M.E. has different diagnostic criteria to chronic fatigue syndrome; neurological symptoms are required but fatigue is an optional symptom.Cite error: Closing </ref> missing for <ref> tag

Antibodies or immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response. [2]

Antibodies or immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response. [3]

The information provided at this site is not intended to diagnose or treat any illness.
From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history.