Looking for answers to ME riddle

by Teresa Grøtan in Research 25 March 2015

What exactly is ME? And how can the disease be treated? Kavli Fund supports cancer researchers at Haukeland in their pursuit of the answer.

Overlege Øystein Fluge and head of the cancer ward and Professor Olav Mella has previously conducted several studies of cancer drug rituximab on ME patients. The results of the preliminary final study is submitted for assessment in a medical scientific journals.

PHOTO: Department and Professor Olav Mella, national project coordinator and nurse Kari Sørland and physician and cancer researcher Øystein Fluge trying to figure out what they, and how the disease can be treated. Their hypothesis is that it is a variant of an autoimmune disease that affects the body’s ability to control blood flow.

Holes in medical science

ME is a hole in medicine that we will be to seal, and we think we have come a little piece on the way, says Øystein Fluge.

Fluge tells patients receiving lactic pain of holding a book, which feel as if they have sprung marathon when they try to go to your mailbox, or describing fog sensation in the brain after mental strain. Patients who did not have any effect of sleep or rest.

It surprised us when we became aware of this disease, which like the patients are actually in clinical appearance. It causes us to believe that there is a common disease mechanism behind, and that it is possible to track down. There is a lot of momentum in our project, says Olav Mella.

Genetic predisposition

Mella, Fluge and national project coordinator and nurse Kari Sørland think ME is a variant of autoimmune disease, ie a disease where the body attacks itself.

We believe that it is an auto-reactive response, often after an infection, which in one way or another disrupts the body’s ability to fine-tune blood flow, says Fluge.
An indication of this is that the blood vessels in ME patients not expand as much as in healthy after completing a test where blood vessels are squeezed together.

Researchers also believe that there is a genetic predisposition to ME.
We see that there is an accumulation in some families. Among those who participated in the first study, 45 percent of autoimmune diseases in immediate family. This is higher than in the general population, says Fluge.

Two new studies

Now the team at Haukeland started to test rituximab in a large, randomized test over three years in five treatment centers in the country. 152 ME patients in the study, which is called double-blind, meaning that neither the patient or treat know about infusing the patient receives is saline or medicine.

The three are excited about the result, but equally excited they are the results of another survey they also initiate this year with another cancer medicine, chemo cyclophosphamide.

The reason they want to try out this medication is that two breast cancer patients who also had prolonged ME, experienced a great improvement in the ME disease after they received chemo because of cancer.

Following these observations doctors gave cyclophosphamide three ME patients without cancer. Two of them got a significant improvement. One of these was largely bedridden. Before treatment, view a bracelet registration that she averaging walked 326 steps a day. After six infusions of cyclophosphamide showed registration that she walked 13,000 steps a day.

We do not know whether she is representative of a larger group of ME patients, but we believe that the observations can justify a clinical trial, says Fluge

A new study using cyclophosphamide with six infusions, and with follow-up of 12 months, has just been approved by the Ethics Committee and the Medical Products Agency. The three stressed that they have already found the patients who will participate.

We have received letters from various parts of the world to participate in this survey. I keep getting SMS and emails from desperate people who ask for help, telling Fluge.

Want to reach the very sickest

40 patients, all moderately or severely ill ME, will try out the medicine. At least 25 patients will be “new”, without prior rituximab treatment, while up to 15 may have gotten rituximab earlier, either without response or relapse.

Can we have a minimum 40 percent response rate among the 25 patients who have not received treatment earlier, it is appropriate to start the second part of the study, where we will try the treatment of patients who are so ill that they for years have remained at home or in nursing homes complete darkness and silence, telling Fluge.

This part of the study is conceived as a collaboration between Haukeland University and healthcare close to the patient home.

Kavli Trust supports cyclophosphamide study with a 50 percent nursing position for 12 months. Fund also finances the laboratory work related to both rituximab- and cyclophosphamide studies. The blood tests of all patients. The samples are analyzed and submitted to a biobank.

Will understand disease mechanism

The researchers also conducted three autopsies of people who suffered from ME.

We are trying to understand disease mechanism. Intellectually, this work is just as interesting as watching response to disease treatment. It is this that can remove the whole management of the disease and the patient group, says Olav Mella.

Scientists estimate that 0.1-0.2 percent of the population affected by ME. They differ between ME, defined by so-called Canadian criteria, and fatigue and burnout that can befall ten times more of the population. They think a lot of disagreements that have emerged in the media due to the unclear boundary of what is what.

It is fascinating with which security some claim that they know what ME is. We do not know what ME is. We have some hypotheses, but we do not know. There is no proof of what ME is due. Then it is interesting that some ignore the patients themselves talk about their illness, says project coordinator Kari Sørland.

We can understand that one can disagree our hypothesis for ME disease. However, it is incomprehensible that one does not want that research and conducted clinical trials, as long as these are thoughtful and performed by international guidelines, says Fluge.

From faker’s disease plaque in the brain

ME is not the first disease in history where the sick have not been believed. Multiple sclerosis (MS) was called faker’s disease until the MRI apparatus was invented and found plaques in the brain. Ulcers believed came because of stress, until it was discovered a bacterium in the stomach.

Because of the high costs it is rare that such large trials that the new rituximab study researcher driven and not initiated and run by pharmaceutical companies. The research team has received support from the Ministry of Health, the Research Council, ME Association, fundraising  and You besides Kavli Fund.