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Øystein Fluge

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history
Source:InvestinME
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 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

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

Notable ME/CFS Studies

  • 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] - (Full text)
  • 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] - (Full text)
  • 2019, Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome[18] - (Full text)
  • 2020, Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)[19] - (Full text)
  • 2020, Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study[20] - (Full text)

See also

Learn more

References

  1. ↑ "Øystein Fluge, MD, PhD & Olav Mella, MD, PhD". Open Medicine Foundation. Retrieved October 10, 2019.
  2. ↑ "ME/CFS research". Helse Bergen (in norsk). Retrieved October 10, 2019.
  3. ↑ "OMF grants $1.2M to Ramp Up Collaborative Research Center at Stanford University". bos.etapestry.com. Retrieved September 12, 2019.
  4. ↑ "Invest in ME Research - International ME Conferences and Colloquiums Home Page". investinme.org. Retrieved September 12, 2019.
  5. ↑ "RituxME". Helse Bergen. Retrieved September 10, 2019.
  6. ↑ "Norwegian Rituximab Chronic Fatigue Syndrome (ME/CFS) Trial Fails". Simmaron Research. November 26, 2017. Retrieved September 12, 2019.
  7. ↑ "European ME Alliance - Norway's Directorate of Health Apologises to ME Patients for Poor Treatment". euro-me.org. Retrieved September 12, 2019.
  8. ↑ "CycloME part A". Helse Bergen (in norsk). Retrieved October 10, 2019.
  9. ↑ "CycloME part B". Helse Bergen (in norsk). Retrieved October 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 (July 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 4488509. 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 (August 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. (October 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. (November 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 (April 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.
  19. ↑ Lande, Asgeir; Fluge, Øystein; Strand, Elin B.; Flåm, Siri T.; Sosa, Daysi D.; Mella, Olav; Egeland, Torstein; Saugstad, Ola D.; Lie, Benedicte A. (March 24, 2020). "Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)". Scientific Reports. 10 (1): 1–8. doi:10.1038/s41598-020-62157-x. ISSN 2045-2322.
  20. ↑ Rekeland, Ingrid G.; Fosså, Alexander; Lande, Asgeir; Ktoridou-Valen, Irini; Sørland, Kari; Holsen, Mari; Tronstad, Karl J.; Risa, Kristin; Alme, Kine; Viken, Marte K.; Lie, Benedicte K.; Dahl, Olav; Mella, Olav; Fluge, Øystein (2020). "Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study". Frontiers in Medicine. 7: 162. doi:10.3389/fmed.2020.00162. ISSN 2296-858X. PMC 7201056. PMID 32411717.
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