Jennifer Molson recalls reading through a thick stack of consent forms before participating in a risky, new stem-cell transplant study. Every other paragraph seemed to warn that the experimental treatment for multiple sclerosis could lead to her death.
The procedure, which wipes out one’s immune system with chemotherapy before replacing it using transplanted stem cells, left Ms. Molson sick and vomiting for nearly a year.
But it worked. Today, nearly 17 years after participating in the study at the Ottawa Hospital, she can work, drive, ski and kayak – all without drugs.
Now a new international study published Tuesday provides more evidence that stem-cell transplants can halt the progression of MS in certain patients, using an approach that is less aggressive than the one used on Ms. Molson. The U.S.-led study, published in the American Medical Association journal JAMA, is the first large, randomized trial to compare stem-cell transplantation with conventional MS drugs. The result: Stem-cell transplantation was more effective among the study’s 110 patients in the United States, Britain, Sweden and Brazil.
Lead author Richard Burt, a professor of medicine and chief of the division of immunotherapy at Northwestern University, says he anticipates other researchers will now try to confirm these findings with further studies.
“Hopefully they will, and that will fundamentally change the field in the history of this disease,” Dr. Burt says. But for now, he cautions the treatment is still risky, and is not appropriate for all MS patients.
Canada has among the highest rates of MS in the world, affecting an estimated 77,000 adults aged 20 and older. MS is considered what’s called an immune-mediated disease, in which the body’s defence system attacks and damages the myelin, or protective coating around nerve fibres. The disease is unpredictable, it affects patients differently and the cause is unknown. Frustrated by standard treatments, which comprise mainly medications and rehabilitation therapies, some patients have turned to unproven remedies, including “liberation therapy,” made famous by Italian surgeon Paolo Zamboni. A large-scale Canadian trial has since shown that the therapy is ineffective, and Dr. Zamboni himself published a paper last year showing it does not improve patients’ ability to function.
In the early stage of the disease, many MS patients experience episodes of acute inflammation in the brain and spinal cord, causing attacks called “relapses,” where their symptoms flare up and eventually either partially or completely subside. But damage can accumulate with further relapses. And even when a patient no longer experiences relapses, he or she tends to become more disabled over time, a second stage of the disease known as “progression,” explains Harold Atkins, a stem-cell transplant physician and scientist at the Ottawa Hospital and associate professor at the University of Ottawa.
Although multiple drugs are available to manage MS, only one offers some hope of treating the progression, says Dr. Atkins, who was part of the team that performed the stem-cell transplant on Ms. Molson.
This is where stem-cell transplantation shows promise. The procedure involves harvesting the patient’s hematopoietic stem cells (stem cells that live in bone marrow) and treating the graft to get rid of any contaminating immune cells. Then, chemotherapy is used to knock out the existing immune system before reintroducing the graft to the body, where the stem cells regrow the immune system.
In an editorial for JAMA, Dr. Atkins noted that the latest study led by Dr. Burt shows results in favour of hematopoietic stem-cell transplantation for patients with very active MS, who have frequent relapses (relapsing-remitting MS). Three patients who received a transplant experienced disease progression, compared with 34 patients treated with conventional drugs. The stem-cell transplantation group also experienced other advantages, including fewer relapses, a greater likelihood of seeing their disabilities stabilize or improve and a better quality of life.
“It’s a very powerful demonstration [in] those patients with very aggressive multiple sclerosis that a stem-cell transplant changes the course of the disease,” says Dr. Atkins, who was not involved in the study. “It’s really the only treatment that we’ve seen that really puts the brakes on progression.”
However, researchers and doctors are still learning about which types of patients would benefit most from stem-cell transplantation, Dr. Atkins says. Conventional treatments, including newer, more effective drugs, can work very well for many patients and are less risky, he says. Stem-cell transplantation has been shown to work best on those who experience many relapses early on, who become disabled soon after diagnosis and who do not respond to standard drugs.
Furthermore, there are differing approaches to stem-cell transplantation for treating MS, and researchers have yet to directly compare them.
Researchers at the Ottawa Hospital and the University of Manitoba are also involved in an international trial that is testing the efficacy of transplants using mesenchymal stem cells, which can come from many different tissues, and are isolated and grown in a culture before they are injected into the patient. The process does not require chemotherapy, and when conducted at academic centres that use high-quality standards, there have not been major side effects, Dr. Atkins says.
However, he cautions, there is no strong proof yet that mesenchymal stem-cell transplants work. And he warns that some private clinics offering mesenchymal stem-cell transplants have led to significant problems in patients.