Principal Investigator

Prof. David Patrick

Institution

School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, USA

In many cases, the drugs used to treat various diseases are effective in only a proportion of patients. It can therefore be valuable to identify these individuals, so that those unlikely to benefit can be spared unnecessary treatments and potential side-effects.

Rituximab is an antibody that attacks B-lymphocytes, a type of white blood cell. The drug has been used to treat some cancers and autoimmune disorders, and a scientific report in 2011, by Øystein Fluge and Olav Mella of the Haukeland University Hospital in Bergen, suggested that the symptoms of ME/CFS could be improved by treatment with rituximab.

The results of their study showed “lasting improvements in self-reported fatigue” over 12 months of follow-up in 67% of ME/CFS patients on rituximab, compared with a response rate of 13% among those on placebo. Rituximab was also associated with significant improvements in some quality-of-life measurements, and there were no serious adverse events.

The investigators subsequently reported promising results in another group of ME/CFS patients, in a study designed to explore the effects of rituximab over a longer period. They are now working on a randomized, placebo-controlled trial of the drug at five centres in Norway.

The Norwegian team has also been keen to collaborate with researchers around the globe, and has established contacts with the group led by Prof. David Patrick at the School of Population and Public Health, University of British Columbia. In 2015, Prof. Patrick received a grant from ME Research UK to help examine the post-exercise fatigue and malaise of ME/CFS patients using newly available gene sequencing technologies, and this work is well underway.

Another of his group’s specialities, however, is the development of immunosignatures. An immunosignature uses an array of chemical compounds called peptides to give information about the antibodies present in an individual’s blood.

Prof. Patrick acquired some samples from the Norwegian team with which to develop an immunosignature capable of distinguishing ME/CFS patients likely to respond to rituximab treatment from those who will not. This issue is important because rituximab is associated with potentially serious side-effects and requires clinical monitoring, and it is also an expensive drug.

The preliminary results were promising (200 peptides differentiated responders from non-responders 92% of the time), so ME Research UK has awarded Prof. Patrick a grant to see if the results can be confirmed in a blinded study using a larger number of samples from all 152 patients taking part in the Norwegian randomized trial.

If the immunosignature pattern for the clinical response to rituximab is found to be sufficiently sensitive and specific, it may represent a useful biomarker for ME/CFS patients’ responses, helping to predict those who will and those who will not benefit from rituximab treatment.