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BBB seminar: Øystein Fluge

B-lymphocyte depletion and disease mechanisms in myalgic encephalopathy/chronic fatigue syndrome (ME/CFS)

Øystein Fluge
Department of Oncology and Medical Physics, Haukeland University Hospital

Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease of unknown etiology, affecting approximately 0.2% of the population thus estimated to affect 15 millions worldwide. ME/CFS is 3-4 times more prevalent in women than in men, and is associated with a very low quality of life for patients. Due to lack of knowledge on the disease mechanisms no effective standard treatment exists.

At the Department of Oncology, Haukeland University Hospital, we observed patients with longstanding ME/CFS who got lymphoma, and who experienced relief of ME/CFS symptoms after either chemotherapy or the therapeutic monoclonal anti-CD20 antibody rituximab. We hypothesized that ME/CFS may be a variant of an autoimmune disease, in a subgroup with a central role for B-lymphocytes and possibly antibodies. We have evaluated B-lymphocyte depletion as a therapeutic principle in ME/CFS, first in a case series, followed by a small randomised and placebo-controlled trial, and then an open-label phase II trial with rituximab maintenance therapy, with the pooled experience suggesting a therapeutic benefit. To either verify or refute the findings from previous studies, a national, multicentre, randomised, double-blind and placebo-controlled phase III trial is ongoing, evaluating rituximab (or placebo) maintenance therapy in ME/CFS (RituxME), with 151 patients included. Also, an open-label phase II study evaluating cyclophosphamide infusions in 40 patients with ME/CFS (CycloME) is ongoing, based on observations of several patients with long-standing ME/CFS who got breast cancer with adjuvant chemotherapy and who reported major ME/CFS symptom relief, and experiences from pilot ME/CFS patients receiving cyclophosphamide infusions. We perform laboratory work using biobank material from patients included in the clinical trials, with the aim to elucidate disease mechanisms. We recently published an article suggesting that ME/CFS is associated with an impaired pyruvate dehydrogenase (PDH) function, resulting in lack of fuelling of the tricarboxylic acid (TCA) cycle from glycolysis, with subsequently lack of energy (ATP) and early accumulation of lactate upon limited exertion, and use of alternative substrates for TCA oxidation.
 

Chairperson: Karl Johan Tronstad <karl.tronstad@uib.no>, Department of Biomedicine