An anti-cancer drug could hold the key to treating chronic fatigue syndrome (CFS). Symptoms of the disease eased in 10 of 15 patients given rituximab, an anti-lymphoma drug.
Rituximab works by destroying white blood cells that make antibodies, called B cells. The results of the trial therefore strongly suggest that these white blood cells might be involved in causing CFS – a disorder also known as "yuppie flu" or myalgic encephalomyelitis (ME), and one that has so far defied explanation.
The research was jointly led by Øystein Fluge and Olav Mella at the Haukeland University Hospital in Bergen, Norway. Their team discovered by accident that rituximab might work against CFS after seeing symptoms ease in a patient who had both lymphoma and CFS.
"We think it affects all symptoms [of CFS], so it must touch the central pathological mechanism causing the disease," Fluge says.
Two of the 15 people in the trial appear to have completely recovered since they first received the drug three years ago. "Those two are both back at work," Mella says.
"It's the most encouraging drug result so far in the history of this disease," according to Charles Shepherd, medical adviser to the UK ME Association. "Although it's a small trial, it's produced dramatic results."
The researchers say that following two doses of the drug being given in the first two weeks of the trial, there was a lag of three to eight months before symptoms began to subside. They say this delayed response tallies with the idea that CFS is caused by autoantibodies – antibodies, made by B cells, that mistakenly attack the body's own tissues.
Rituximab is itself an antibody designed to target and destroy B cells. Mella says that all the B cells are gone within two weeks or so of the treatment, but autoantibodies typically survive in the body for another two or three months. "Washing out these antibodies is the most probable explanation for the time lag in benefits," he says.
The researchers found no trace of XMRV, a mouse leukaemia virus once implicated as a possible cause of CFS. The virus has now been virtually eliminated as a possible cause.
"We looked as hard as we could for it, by several methods, but the search was negative," Fluge says. "We think suggestions it was XMRV [causing CFS] have turned out to be a blind alley, caused by contamination of samples."
Last month, one of the authors of the 2009 paper that implicated XMRV retracted his data from that study after acknowledging that the virus was present through contamination.
"XMRV is dead, a sad and disappointing story that raised a lot of false hopes for patients," says Shepherd. He adds that it is important not to raise hopes again by over-hyping the rituximab results. "We're still a long way from making this drug more widely available, but if someone wants to mount a UK trial, we'd look at that," he said.
Encouraged by the extended remission of two of the people in the trial, the Norwegian researchers are now checking whether further, periodic doses of rituximab could permanently keep the symptoms of CFS at bay. Mella says it is possible that the five who saw no benefits from the trial might have done so eventually if they had received further doses.
Journal reference: PLoS ONE, in press
European ME Alliance Welcomes Ground-breaking research from Norway -
The European ME Alliance welcomes the research by Fluge, Mella et al published on 19th October 2011 in Plos One.
This research clearly shows the physical basis of ME.
It also shows that patients had no difficulty in adjusting to normal life - something which makes redundant the previous attributions to psychological problems in this patient group.
Now we encourage public funding bodies in different countries to follow the example of this double blind placebo controlled clinical trial to start seriously investing in biomedical research into ME.
It is time to take this disease seriously and help patients regain their health and normal functioning.
European ME Alliance