Olav Mella

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Olav Mella is an Adjunct Professor in 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 Dr. Øystein Fluge in the Norwegian Rituximab and cyclophosphamide trials for the depletion of B cell lymphocytes in ME/CFS patients.

Dr. Mella is a member of the Working Group which offers their expertise and resources to the ME/CFS Collaborative Research Center at Stanford University.[1]

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

Øystein Fluge's and Olav Mella's discovery was found by accident, in that 3 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 are 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.[2] The clinical trial, named RituxME, is now a multicenter, phase III study. It is 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). Results will be published in 2018.[3]

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.[4]

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.[5]

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.[6]

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[8] - (Full Text)
  • 2015, B-lymphocyte depletion in myalgic encephalopathy/chronic fatigue syndrome. An open-label phase II study with rituximab maintenance treatment[9](Full Text)
  • 2016, Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome[10](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.[11]
  • 2016, Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome[12] - (Full Text)
  • 2018, Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)[13](Full text)
  • 2018, Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome[14](Abstract)
  • 2019, B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial[15]
  • 2020, Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)[16] - (Full text)
  • 2020, Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study[17] - (Full text)
  • 2021, Fine mapping of the major histocompatibility complex (MHC) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggests involvement of both HLA class I and class II loci[18](Full text)

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. ↑ "OMF grants $1.2M to Ramp Up Collaborative Research Center at Stanford University". bos.etapestry.com. Retrieved May 6, 2020.
  2. ↑ Invest in ME Research. "Invest in ME Research - IIMEC7 International ME Conference 2012". Invest in ME Research. Retrieved May 6, 2020.
  3. ↑ http://www.helse-bergen.no/en/OmOss/Avdelinger/kreft/forsking-fagutvikling/Sider/RituxME.aspx
  4. ↑ Simmaron Research (November 26, 2017). "Norwegian Rituximab Chronic Fatigue Syndrome (ME/CFS) Trial Fails". Simmaron Research. Retrieved May 6, 2020.
  5. ↑ European ME Alliance. "Norway's Directorate of Health Apologises to ME Patients for Poor Treatment". euro-me.org. Retrieved May 6, 2020.
  6. ↑ http://www.helse-bergen.no/en/OmOss/Avdelinger/kreft/forsking-fagutvikling/Sider/CycloME.aspx
  7. ↑ Invest in ME Research. "IIMEC12 International ME Conference 2017". Invest in ME Research. Retrieved May 6, 2020.
  8. ↑ 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.
  9. ↑ 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
  10. ↑ 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.
  11. ↑ 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
  12. ↑ 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. PMID 26399744.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ Hajdarevic, Riad; Lande, Asgeir; Rekeland, Ingrid; Rydland, Anne; Strand, Elin B.; Sosa, Daisy D.; Creary, Lisa E; Mella, Olav; Egeland, Torstein (November 1, 2021). "Fine mapping of the major histocompatibility complex (MHC) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggests involvement of both HLA class I and class II loci". Brain, Behavior, and Immunity. 98: 101–109. doi:10.1016/j.bbi.2021.08.219. ISSN 0889-1591.

B cell B lymphocyte, or a type of white blood cell, which is involved in the immune response by secreting antibodies to ward off infections. In mammals, they are mostly matured in the bone marrow.

phase three Last phase of clinical trials before a drug can be approved for public use. Whereas Phase one assesses basic safety, and Phase two assesses basic efficacy, Phase three uses many trial participants to fully assess both safety and efficacy, and overall benefit/risk.

double blinded trial A clinical trial is double blinded if neither the participants nor the researchers know which treatment group they are allocated to until after the results are interpreted. This reduces bias. (Learn more: www.nottingham.ac.uk)

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

myalgic encephalopathy An alternate term that is sometimes used for myalgic encephalomyelitis, by people who believe the evidence for inflammation in ME is insufficient. This terminology reflects the belief that the "-itis" suffix implies inflammation.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

phase two A trial involve patients to assess side effects and effectiveness for a particular clinical condition. Typically 100-300 patients.

serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

myalgic encephalopathy An alternate term that is sometimes used for myalgic encephalomyelitis, by people who believe the evidence for inflammation in ME is insufficient. This terminology reflects the belief that the "-itis" suffix implies inflammation.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

β β / Β. Greek letter beta (a symbol used in science), equivalent to "b".

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

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