A radical and risky stem cell therapy has been shown to halt and even reverse some of the symptoms of those worst affected by multiple sclerosis, a disease that in many people has proved untreatable.
Doctors in Canada conducted an experimental stem cell transplant with 24 patients who were expected to be confined to a wheelchair within 10 years. After receiving the treatment most of the patients regained control of their lives, becoming able to walk, play sport and drive.
To succeed, the transplant required the destruction and rebooting of each person’s immune system – such a high risk approach that one of the patients died. But the others, followed up for between four and 13 years, had no further progression of the disease. The disease normally entails worsening symptoms over time.
To the surprise of their doctors, some patients recovered functions that had been eroded by the disease, including their sight and balance. Six returned to work or college, five married or became engaged and two had children using banked sperm or eggs, as the aggressive treatment had made them infertile.
Mark Freedman, a neurologist at the University of Ottawa, who co-led the trial, said he would not say his patients were cured. “I hesitate to use the c-word. A cure would be stopping all disease moving forward and repairing all damage that has occurred. As far as we can ascertain no new damage seems to occur beyond the treatment and patients don’t need to take any medication, so in that sense I think it has induced a long-standing remission. Some patients did recover substantial function and it allowed them to do things they couldn’t do for years, but others did not.”
However, the long-term results of the trial in Canada, published in the Lancet medical journal, have been universally applauded by scientists and support groups and will lead to a worldwide clamour for the transplants to be more widely available.
Stephen Minger, a stem cell biologist and independent consultant, said: “The clinical results are truly impressive, in some cases close to being curative, though we need longer-term follow-up to know for certain whether the patients continue to do well or if there is a chance of relapse. And of course this trial will need replication by other groups too.
“For a life-long progressive disease like MS with few treatment options this is really exciting data. It offers the hope of having a long-lasting treatment which may halt disease progression – though, again, this is a very invasive therapy and not without risks. Still I would consider it a breakthrough therapy, and the clinical group and the patients should be congratulated for this success.”
The doctors say this treatment is not for everyone with MS because of the dangers. Modern drugs can control the symptoms for most people with the disease, but they do not work in people who have a sudden onset of very aggressive disease with frequent relapses. Freedman said the transplants they had been doing in Ontario were suitable for perhaps 5-10% of MS patients. “It is needless if the disease can be controlled with mild medicines that don’t carry those kind of risks,” he said.
Multiple sclerosis is caused by a malfunction of the immune system, which ordinarily defends the body against bacteria, viruses and disease. The disease attacks instead the insulating myelin sheath, which is essential for the proper functioning of the nervous system. Those who are badly affected, usually young, progressively lose the ability to control their limbs.
Stem cell transplants have been carried out before in MS patients, but those people had a relapse after a couple of years. Never before have doctors used the aggressive drug regimen used in Canada – a therapy that totally destroys the immune system, putting patients at risk for a while from life-threatening infections.
The patient in the transplant group who died suffered very severe liver damage and a bacterial infection which caused sepsis, or blood poisoning.
In the process, the Canadian doctors removed stem cells from the bone marrow of the patients and processed these in a laboratory. They then used a combination of three toxic drugs to destroy each patient’s immune system before transplanting the cleaned-up stem cells in to the body.
“There were some fairly profound and wonderful changes that some of them experienced,” said Freedman. “Some people hadn’t walked and started walking. Some people who had lost their vision were seeing. More than half the patients returned to gainful employment, maintained their relationships, got back their driver’s licence.”
Some, however, had disease that was progressing “like a runaway train”, he said. They continued to get worse for a couple of years but then their disease also stopped progressing. “But nobody developed any new inflammation at all,” he said. Their brain scans showed no new lesions, he added.
People with MS have been going to clinics in Mexico and elsewhere in the world in search of stem cell treatments they hope will turn out to bring a cure. But doctors emphasised that the regimen used in Canada, being very dangerous, had to be restricted to very specialised centres, and needed to be tested in more people before it became more widely available.
In the UK, Paolo Muraro, a neurologist at Imperial College London, who met Freedman last week to discuss the results, is hoping to start his own international trial, involving about 180 people with MS. That trial would try a slightly less intense drug regime in the hope of reducing the risks, he said. He was still seeking funding for it and said the treatment might have been more widely available by now if it had been a drug.“
The treatment does not rely on any proprietary drug, so it is not a treatment that has received any support from the pharmaceutical industry. People like Mark Freedman and myself have had to work with very limited resources to try to develop this treatment really from charitable funding and academia-driven units.”
The Canadian results were “indeed very good news”, he said, although, he added, it was important to avoid raising false hopes, because of the risks and the need for more trials.
The study in Ontario was funded by the MS Society of Canada. Charities in the UK also welcomed the findings but warned that people with MS who might think of having a stem cell transplant should speak to their doctor.
Emma Gray, head of clinical trials at the MS Society, said: “This treatment does offer hope, but it’s also an aggressive procedure that comes with substantial risks and requires specialist aftercare. If anyone is considering [a stem cell transplant] we’d recommend they speak to their neurologist.”
Amy Bowen, at the Multiple Sclerosis Trust, said the results were “extremely interesting and encouraging”. She added: “Stem cell therapy is still very experimental, and is not suitable for everyone. However, it could be a potentially very effective therapy, holding great promise for people living with MS. It’s also a long way from being a routine treatment for MS.”