What exactly is myalgic encephalopathy (ME), also known as chronic fatigue syndrome (CFS), and how can it be treated? Answers to these questions are being sought by cancer specialists at Norway’s Haukeland University Hospital with support from the Kavli Trust.
By Teresa Grøtan (text and photo)
Senior consultant Øystein Fluge and professor Olav Mella, who heads the hospital’s cancer department, have conducted several studies on treating ME patients with the cancer drug Rituximab. Results from the most recent of these investigations have now been submitted to a medical journal for publication.
From left: Olav Mella, department head and professor, Kari Sørland, national project coordinator and nurse, and Øystein Fluge, senior consultant and cancer scientist, are seeking to establish what ME involves and how it can be treated. Their hypothesis is that the condition represents a form of autoimmune illness which affects the body’s ability to control the blood supply.
“ME represents a gap in medical knowledge which we want to help close, and we believe we’ve made a little progress towards reaching that goal,” says Fluge.
He talks about patients suffering lactic acidosis from holding a book, who find a walk to the post box feels like running a marathon, whose brain goes foggy after mental exertion, or who get no benefit from sleep or rest.
“What surprised us when we came across this condition was how similar the sufferers actually were in their clinical presentation,” adds Mella.
“This leads us to think that a single underlying causal mechanism is at work, which it should be possible to track down. That thought provides much of the drive behind our project.”
Mella, Fluge and nurse Kari Sørland, who is national coordinator for the work, believe that ME is a form of autoimmune illness where the body comes under attack from its own defence system.
“We think an autoimmune response, often after an infection, somehow disrupts the body’s ability to micro-manage the bloodstream,” Fluge explains.
One indication that this might be the case is that blood vessels in ME patients do not enlarge as far as in healthy people after they have been compressed.
The researchers also believes that sufferers have a genetic predisposition to develop ME. Fluge notes that the condition tends to run in certain families.
“Members in the immediate family of 45 per cent of the participants in our first study had autoimmune illnesses. That’s a higher proportion than in the general population.”
The Haukeland team is now subjecting Rituximab to a large randomised test running over three years at five treatment institutions in Norway.
Involving 152 ME patients, the trial is double-blind – in other words, neither recipient nor tester knows whether the infusion given consists of a saline solution or the medication.
While the trio are eagerly awaiting results from this test, they are equally interested in the outcome of another trial to be launched in 2015 with the Cyclophosphamide chemotherapy drug.
The background for testing this treatment is that two breast cancer victims who also had long-term ME experienced a big improvement in the latter condition after chemotherapy.
That prompted the physicians to give Cyclophosphamide to three ME sufferers who did not have cancer. Two of them experienced a substantial improvement – including one who was largely bedridden.
Before treatment, the latter walked a measured average of 326 steps per day. After six infusions with Cyclophosphamide, she was able to take 13 000 daily paces.
“We obviously don’t know whether she’s representative of a large group of ME patients,” observes Fluge. “But we believe these observations justify a clinical study.”
A new trial based on six Cyclophosphamide infusions followed by 12 months of monitoring has just been approved by an ethics committee and the Norwegian Medicines Agency.
The trio reports that they have already identified the participants. “We’ve had letters from various parts of the world asking to join the trial,” says Fluge. “I’m constantly getting texts and e-mails from desperate people asking for help.”
Forty patients with moderate or serious ME will take part. At least 25 will be “new” – not treated earlier with Rituximab – while up to 15 may have received that medication earlier without response or with a relapse.
“A minimum response rate of 40 per cent among the 25 sufferers who haven’t had Rituximab before would permit us to move to the second phase of the study,” explains Fluge.
“That’ll investigate treatment of people who’re so ill that they’ve lain in complete darkness and quiet for many years at home or in a nursing home.”
This part of the study is expected to involve a collaboration between the Haukeland hospital and health services close to the patient’s home.
The Kavli Trust is supporting the Cyclophosphamide trial by funding 50 per cent of a nursing post for 12 months.
It will also finance laboratory work related to the Rituximab and Cyclophosphamide studies. Blood samples from all the patients are to be analysed and stored in a blood bank.
The researchers have conducted three autopsies of people who have suffered from ME, reports Mella. He explains that the aim is to understand the mechanism of the illness.
“Intellectually, this work is at least as interesting as observing the response to treatment. It could help to solve the whole question of treatment for these patients.”
The team calculates that 0.1-0.2 per cent of the Norwegian population are affected by ME – defined by “Canadian” criteria, which exclude the tiredness and exhaustion experienced by 10 times that number.
In their view, much of the disagreement which has surfaced in media coverage reflects unclear delimitation between different conditions.
“It’s fascinating to see the absolute conviction of some people who claim to know what ME is,” says Sørland. “Nobody has any proof of its cause. It’s interesting that some people ignore what the patients themselves say about their illness.”
“Others may well disagree with our hypothesis,” emphasises Fluge. “What’s incomprehensible is that people don’t want research and clinical studies conducted on a well-considered basis and in accordance with international guidelines.”
ME is not the first medical condition where sufferers have been disbelieved. Multiple sclerosis, for example, was among the illnesses known as “faker’s disease” until magnetic resonance imaging disclosed plaques in the brain.
And many people maintained that ulcers were caused by stress – until the guilty bacterium was discovered in the stomach.
Because of the big costs involved, a trial as large as the latest Rituximab study is seldom staged by researchers rather than the big pharmaceutical companies.
The Haukeland team has received support from the Norwegian Ministry of Health, the Research Council of Norway, the national ME association and the MEandYou crowdfunding appeal as well as the Kavli Trust.