By Øystein Fluge, Karl Johan Tronstad and Olav Mella

Photo: Øystein Fluge, senior consultant and cancer scientist and Karl Johan Tronstad, professor.

The Kavli Trust has supported ME research at the oncology department at Haukeland University Hospital since 2011. The cooperation with the Kavli Trust has enabled the group to engage in new projects and make scientific advances in the field of biomedical research on ME/CFS.

Photo: Olav Mella, department head and professor and Kari Sørland, national project coordinator and nurse.

Previously, the research group has published clinical studies investigating the use of the immune drug Rituximab in patients with ME/CFS ([i], [ii], [iii]). Rituximab is an artificially manufactured antibody which reduces the number of B-lymphocytes, a type of white blood cells which can develop into immune cells with a number of functions, among them antibody-producing cells. These studies have shown symptom improvement in approximately 60 % of patients treated with the drug. We hypothesize that ME in a subgroup of patients could be a type of immunological disease, in which B-cells and possibly adverse effects of antibodies play a part.

Confirm or refute

Five Norwegian hospitals are now collaborating on a clinical trial aiming to confirm or refute whether Rituximab can be useful in the treatment of ME patients. At Haukeland, the research group is also conducting a trial of moderate doses of the chemotherapy drug Cyclophosphamide, which has immunosuppressive effects and targets more parts of the immune system than the more specific Rituximab. Through these clinical studies, we are aiming to uncover possible treatment methods, while simultaneously working to shed light on the underlying symptom mechanisms in ME.

Biochemical changes

More than 200 patients have been included in our studies after thorough medical assessment according to internationally accepted («Canadian») criteria. These patients are subject to systematical and standardized follow-up in the studies, and regularly donate blood samples to a research biobank. Based on the material collected in the biobank, the research group has conducted a comprehensive and detailed mapping of the metabolism in 200 patients and 100 healthy controls. The project was supervised by the authors (Karl Johan Tronstad, Øystein Fluge and Olav Mella), and conducted in collaboration with Bevital AS and Per M. Ueland.

As a result of these metabolic analyses, we detected specific biochemical changes in the blood of ME/CFS patients. These findings have now been published in the Journal of Clinical Investigation Insight.

The analyses of blood samples from the ME/CFS patients showed that the levels of certain amino acids were reduced compared to healthy control subjects. The pattern of amino acid changes gave us important information about the symptom mechanisms, and in particular about the patients’ energy metabolism.

May explain energy deficiency

Under normal circumstances, human cells utilize carbohydrates, fats (lipids) and proteins (amino acids) as sources of energy, through catabolic processes in the mitochondria, the “powerhouses” of the cell. However, when we engage in intense physical exercise, there is a shortage of oxygen delivered to the muscle mitochondria (anaerobic exercise), at which point glucose is converted to lactic acid. Since lactate accumulates and there is lower energy yield, the body will say “stop” after a short time. The enzyme pyruvate dehydrogenase (PDH) plays an important role in the regulation of these processes, as it contributes to coordinating the utilization of carbohydrates, amino acids and lipids (fats) as energy sources. The new study suggests that the PDH enzyme is inhibited in ME/CFS patients, which may explain both energy shortage and increased lactate production in these patients.