Olav Mella

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.

Rituximab work in ME/CFS
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. 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.

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

 * 2011, 6th Invest in ME International ME Conference 2011 - B-cell Depletion Therapy Using Rituximab in ME/CFS - Part I
 * 2012, 7th Invest in ME International ME Conference 2012 - B-cell Depletion Therapy Using Rituximab in ME/CFS - Part I
 * 2013, 8th Invest in ME International ME Conference 2012 - B-cell Depletion Therapy Using Rituximab in ME/CFS - Part I
 * 2014, Olav Mella speaks about the Rituximab study and ME/CFS future
 * 2015, The Naked Scientists Podcast -"Is ME an autoimmune disease?"
 * 2015, 10th Invest in ME International ME Conference 2015 - no speech title given
 * 2 Jun 2017, Speaker at the 12th Invest in ME International ME Conference on "Update on the clinical trials RituxME and CycloME" DVD available

Notable ME/CFS Studies
(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 (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
 * 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.
 * 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
 * 2020, Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - (Full text)
 * 2020, Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study - (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 (Full text)

Learn more

 * 2015 Fluge & Mella’s pre-trial study highlights life-changing potential of rituximab