New remarkable study shows that stem cells can reverse MS in some patients • Good Assurance

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By the time Amanda Loy turned 28, her multiple sclerosis had progressed to the point that she could no longer work full time. Her hands and legs were numb all the time, her bladder was still full and she had to rely on a cane to walk more than 10 minutes. After giving birth to a son a year later, in 2008, the symptoms worsened. That's when she decided to travel from her home in Anchorage, Alaska, to Chicago to find out about a new treatment she had heard about at a Seattle hospital.

Nearly twelve years later, Loy is now back full-time as a teacher in the University of Alaska's radiology program. She runs half marathons and plays football with her 10-year-old son. She is not taking any more medication for MS. His only persistent symptom is mild nerve pain from time to time.

"It sounds so dramatic, but [the treatment] I've given my life back, "she said.

Treatment consists of experimental chemotherapy and hematopoietic stem cell transplantation as proposed in the first randomized trial comparing outcomes of patients receiving treatment to those taking standard MS drugs.

The results of the trial appeared Tuesday in the newspaper JAMA, and they are impressive: of the 55 patients in the control group who took medication, 34 saw their disease worsen. But for the 55 (including Loy) who received chemotherapy and stem cell transplantation, only three got worse. Others saw their quality of life and disability improve.

This is the best evidence to date that the treatment works for patients with so-called "recurrent" MS. "I think this will change the natural history of MS," said Richard Burt, stem cell researcher at Northwestern University, lead author of the study and Loy's physician. "When you use it in the right group of MS patients, you get these results really rewarding."

Doctors still do not know if the therapy will work for people with other forms of MS. They do not know if the risks of a transplant (including death) will always outweigh its benefits. Nevertheless, dramatic shifts for patients with MS are rare – and deserve to be examined.

Physicians participating in the trial did not expect such dramatic improvements in patients treated with stem cell therapy

MS affects about 2.3 million people worldwide, especially women in more temperate climates such as Canada and the northern United States.

Instead of protecting the body against foreign invaders, in patients with multiple sclerosis, the immune system activates its host, particularly damaging myelin, a protective coating around the nerve fibers of the brain and spinal cord.

Ultimately, these attacks can severely damage and destroy the nerves and myelin, thereby interrupting communication between the brain and the body and causing symptoms such as numbness, difficulty walking and even blindness.

But not all patients' symptoms manifest themselves in the same way. People with "recurrent" MS – or 85% of people with MS – suffer from it intermittently: their symptoms appear for a few days or weeks, followed by weeks, months, or even remission.

For most patients with this version of the disease, these periods of remission gradually diminish over time and eventually disappear, which places them in another phase of the disease called "secondary progressive MS".

Loy and the other patients participating in the trial had relapsing remitting multiple sclerosis. Loy had tried drugs and nothing worked.

Burt told her that the best she could hope for from the stem cell transplant was that her symptoms do not get worse. "I did not really expect all these improvements. I went there thinking, "If at least I do not get worse from now, it'll be fine," she said. "All the improvements have been totally unexpected, but a good surprise, that's for sure."

Amanda Loy with her son during his treatment. Courtesy of Amanda Loy

How stem cells rebuilt Loy's immune system

The route to Loy's stem cell transplant was not simple. She learned about the approach two years after her diagnosis and contacted a Seattle hospital to inquire about another similar study in 2010. "They were not taking new patients, but they told me that There is a guy in Chicago on whom I could look. in, she says.

This guy was Burt, in Northwestern. She went to meet her in 2010 and discovered that she had qualified for her studies. But she was randomly assigned to the control group – and at first she did not follow the treatment.

In less than two years, however, her MS symptoms worsened. Burt asked her to return to Chicago to assess her disability and decided that she could be transferred to the treatment group. In 2012, she went to Chicago for a transplant.

The treatment consisted of four main steps: The doctors first prescribed short-term chemotherapy to stimulate the production of hematopoietic stem cells, cells responsible for the regeneration of the immune system. They then hooked Loy to a machine that circulated his blood to collect the stem cells, which were frozen. Another higher dose of chemotherapy destroyed Loy's immune system.

"I had difficulty with chemo," recalls Loy. "It really made me very sick and very miserable – nausea, vomiting."

Then, his stem cells were thawed and transplanted into Loy, as a blood transfusion. She was so tired of the chemo that she took a nap during the transfusion.

But then, something extraordinary happened: just after getting the transplant, Loy noticed that her bladder symptoms related to MS had disappeared. And with one year, all of his other symptoms – fatigue, heat intolerance, numbness, nerve pain – have improved or disappeared.

The only side effect of the treatment, she said, was temporary menopause during chemotherapy – but it also quickly disappeared and had no effect on her fertility. Common side effects in other patients in the study's transplant group were infections (such as chest colds and urinary tract infections) and electrolyte disturbances. No one died as a result of the transplant.

All patients with MS will not be eligible for this treatment.

The study that gave Loy the opportunity to reverse MS was impressive – a randomized multicentre randomized international trial conducted in four centers: in Chicago, at the NHS Foundation of Sheffield University Hospitals and at the University of Sheffield in England. Uppsala in Sweden and the University of São Paulo in Brazil. Patients were enrolled in each of these hospitals between 2005 and 2016 and monitored for at least one year to see if their disease had progressed.

The study builds on decades of basic research on MS, stem cells and the immune system, including years of experience in the use of treatment in patients with blood and bone marrow cancers, such as leukemia and lymphoma. It also builds on previous research on this approach to treating MS, such as: a rigorous study of 2016 outside Canada in which 70% of 24 patients who received chemotherapy and bone marrow stem cell transplantation experienced progression of their disease stopped or reversed. Specialists at the time described this study as a "miracle".

"It's one of the first pieces of evidence that yes, aggressive MS patients do better after transplant than with standard treatment."

"Everyone hesitates to use the" word c ", but these patients are cured," Michael Rudnicki, Director of the Regenerative Medicine Program and the Sprott Stem Cell Research Center at the Ottawa Health Research Institute, m said in 2016.

This week, I went back to a patient I had profile then Jennifer Molson, who had a reversal as miraculous as Loy (and she was doing well, with no new symptoms of multiple sclerosis). "I just went up six floors in heels because we had a fire alarm," she said.

Previous studies, such as the one in 2016, had followed people with MS who had received the treatment – and had shown equally impressive results – but they lacked a control arm for comparison. And that's what makes this new study special, said Harry Atkins, a physician and stem cell transplant scientist at The Ottawa Hospital in Canada, led the 2016 study.

"This is the best evidence that compares stem cell transplants to standard treatment," said Atkins. "This is one of the first pieces of evidence that, yes, aggressive MS patients do better after transplant than with standard treatment." (Another randomized trial was published a few years ago, but was tainted of methodological problems. "Burt's paper was overcame, says Atkins.)

The new study also focused on the most important outcome in MS: progression of the disease. "They showed that in the study portion treated conventionally, these patients continued to deteriorate compared to transplant patients – many of them stabilized or improved during the period feedback."

But treatment is not for everyone and the study has important limitations. Burt's focus is on the subgroup of multiple sclerosis patients who have had at least two relapses in the past year. "This is clearly beneficial for these patients, but there is no question of whether the risks and benefits balance out in patients with more conventional MS," he said.

Another limitation is that since the design of the study, new drugs against MS have been put on the market. According to Atkins, these medications seem more effective than older medications and may compare favorably with transplants in a comparative study, but this has not been done yet.

In addition, in early studies of stem cell transplantation for multiple sclerosis, 5% of patients died. Over the past five to seven years, this death rate has dropped to 1 to 2% – especially as chemotherapy regimens have become less toxic – "but it's not zero," said Atkins. "This is where the whole idea of ​​matching the risk to the expected result or benefits is important."

So doctors do not know if this benefit-risk ratio makes sense in patients with less aggressive forms of MS (ie, they have fewer relapses) or how long after diagnosis the treatment must be applied.

There is also the problem of access. You can not just go to the doctor and get the treatment; Although the chemotherapeutic drugs used in the trial have all been approved by the FDA, few hospitals in the world have ever used these treatments in MS patients. Patients should generally be eligible for a clinical trial.

Loy's medical care was mainly covered by his health insurance plan, but this was not the case for all patients. And she had to spend about $ 10,000 to $ 20,000 on hotel and travel expenses to Chicago – the type of urban research center that allows many Americans to experiment.

"This study shows a general benefit for patients," Atkins added. "This opens the door for stem cell transplantation to be a more widely applied treatment. But there are many other questions. "