Genetics and stem cells

Risky stem cell treatment 'halts progress of multiple sclerosis'

"New treatment can 'halt' multiple sclerosis, says study," BBC News reports.

The treatment involves effectively destroying the existing immune system and creating a new one using stem cells. But this new treatment carries a high risk of complications.

Multiple sclerosis (MS) is a life-long condition that affects the brain and spinal cord, causing a wide range of symptoms, including problems with arm or leg movement, vision, sensation and balance, and serious disability.

It is an autoimmune disease where the immune system mistakenly attacks healthy cells in the body – in this case, the coating of the nerves (myelin sheath).

In this Canadian study, researchers essentiality destroyed a patient's existing immune system with a very aggressive course of chemotherapy drugs.

They then transplanted stem cells – which have the potential to become any type of blood cell – in an attempt to rebuild an immune system without the flaws that trigger MS.

Of the 24 patients that took part in the study, 70% had no disease activity three years after the transplant, and about a third had sustained improvement in disability status. For example, 16 patients were able to go back to work or college.

One fact to bear in mind, however, is that this was a small study with no comparison group, and one of the 24 patients died after transplant as the result of an infection.

This represents a mortality rate of 4%. Whether or not this was just an unfortunate one-off is unclear.

The risks and benefits of this approach need to be carefully weighed and compared before it can be widely adopted in clinical practice.

Where did the story come from?

The study was carried out by researchers mostly from medical institutions in Canada, as well as three researchers from the Department of Neurosciences, Cleveland, in the US.

It was funded by grants from the Multiple Sclerosis Scientific Research Foundation. Some of the researchers also received personal fees and grants from a number of pharmaceutical and biotech companies.

The study was published in the peer-reviewed journal, The Lancet.

While the UK media was along the right lines reporting news of a 'breakthrough treatment', it is slightly premature considering this is a very small, early stage, study.

The media did, however, go on to highlight that further investigation was needed before this treatment becomes available in clinical practice.

It was also correctly reported that this treatment wouldn't be suitable for many people with less debilitating MS because of the risks it carries.

What kind of research was this?

This phase II trial aimed to assess a new treatment approach of aggressive chemotherapy followed by haemopoietic stem cell transplant (HSCT).

The researchers wanted to see whether this had an impact on clinical relapse and improvements in disability in people with multiple sclerosis.

Haemopoietic stem cells are very early-stage blood cells that can develop into all other types of blood and immune cells.

This study involved autologous HSCT, where stem cells are first harvested from the patient before high-dose chemotherapy is given to deplete the person's own cells.

The harvested cells were then transplanted in the hope this would allow the immune system to be rebuilt without the flaws that trigger MS.

This is an early-stage clinical trial involving a relatively small number of people and no comparison group. It aimed to see whether the treatment is safe and could potentially be effective.

This is important early-stage research designed to see whether the findings are promising, and may pave the way for further investigation in later trials involving more people and comparisons with other treatments or placebo. 

What did the research involve?

The study began in the year 2000, when researchers recruited 24 patients between the ages of 18 and 50 from three hospitals in Canada.

Their disease was defined as having a high probability of significant progression over the next 10 years, having suffered multiple relapses prior to being enrolled in the study.

The patients first had their haemopoietic stem cells harvested, and their immune system was then fully suppressed with aggressive chemotherapy. They then received HSCT two days after their final dose of chemotherapy. 

The main outcome of interest was the proportion of patients who were surviving and free from MS disease activity three years after transplant.

This was assessed by looking at clinical relapse, appearance of new MS lesions on MRI scans, and sustained improvements in disability status.

Of the 24 patients, 21 were followed up to three years, and 13 took part in longer-term follow-up. The average follow-up duration was 6.7 years (range 3.9-12.7).

What were the basic results?

Overall, 17 of the 24 patients (69.9%) achieved activity-free survival three years after transplantation. The remaining seven patients had sustained progression of disability.

Clinical relapses did not occur in any of the 23 surviving patients during follow-up. These results were mirrored by no new lesions being seen on 314 sequential MRI scans overall. And 35% of patients had sustained improvements in their disability status.

One patient died of transplantation-related complications, however. There were also various side effects associated with treatment.

Most patients experienced toxicity effects of varying degrees of severity, and fever and infections were common.

How did the researchers interpret the results?

The researchers concluded: "We describe the first treatment to fully halt all detectable CNS [central nervous system] inflammatory activity in patients with multiple sclerosis for a prolonged period in the absence of any ongoing disease-modifying drugs.

"Furthermore, many of the patients had substantial recovery of neurological function despite their disease's aggressive nature." 


This early-stage trial aimed to look at a new treatment approach for MS, involving aggressive chemotherapy followed by haematopoietic stem cell transplant (HSCT). Researchers then assessed whether this had an impact on clinical relapse and disability.

The study suggests that eliminating an individual's existing "faulty" immune system, and rebuilding it using stem cells, may slow down or completely halt the progression of MS, resulting in an improvement in disability status.

Although the study's findings suggest this could be a potential treatment in the future, the researchers say caution is necessary before it is widely adopted in clinical practice.

This was very early-stage research, with a small sample size and no control group for comparison with those who were treated.

The findings were positive overall, but the retention to longer-term follow-up was quite low, with only around half being followed up beyond three years.

This means although there were no documented relapses and around a third improved functional ability during follow-up, these results could be different with a much larger sample size.

Also, the fact there was one death among the 24 treated patients and toxic side effects were common cannot go unnoticed.

Dr Payam Rezaie, a reader in neuropathology at The Open University, commented: "While this study does add considerable weight to the use of autologous HSCT as a therapeutic approach for MS, it is difficult to make a more generalised inference on its use, based on this study alone.

"The risks need to be carefully weighed when compared with the beneficial outcomes. The present study indicates a need to examine this further."

Further trials in larger groups of people with MS, including those with different disease characteristics, and comparing it with other treatments, would be needed to better gauge the effectiveness and safety of this approach.  

NHS Attribution