MS stem cell treatment only a 'miracle' for some

The Daily Telegraph reports a "miracle" stem cell therapy that reverses multiple sclerosis and which, according to The Sunday Times, gets "wheelchair-bound" people dancing.

Multiple sclerosis (MS) affects nerves in the brain and spinal cord, causing problems with muscle movement, balance and vision. It's an autoimmune disease, where the body's immune system attacks its own nerve cells. There is currently no cure, but many different treatments are available to help with symptoms.

This study was mainly about relapsing-remitting MS, the most common type, where people have distinct attacks of symptoms, which then fade away either partially or completely.

The new treatment was very aggressive. It used high doses of chemotherapy to "knock out" the existing faulty cells of the immune system, before rebuilding it using stem cells taken from the patient's own blood. This, in effect, gave the immune system a chance to reboot from scratch.

The therapy was tested in 145 patients and led to significant reductions in their levels of disability in almost 64% of people up to four years after treatment. Improvements were seen in quality of life and other ratings of symptoms and disability. Because of the difficulty in treating MS effectively, any improvements are good news.

The downside is that there was no control group. We don't know if some people would have improved on their own, or whether the improvements are any better than best available care. It's also worth noting that not everyone will be able to tolerate the aggressive chemotherapy used, and that the technique did not work for people with more severe or longstanding MS (over 10 years).

Find out more about multiple sclerosis.

Where did the story come from?

The study was led by researchers from Northwestern University Feinberg School of Medicine, Chicago, US, and was funded by the Danhakl family, the Cumming Foundation, the Zakat Foundation, the McNamara Purcell Foundation, and Morgan Stanley and Company.

Two study authors declared financial conflicts of interest by serving as consultants to pharmaceutical companies including Biogen Idec, which makes treatments for patients with "neurological, autoimmune and hematological disorders".

The study was published in the peer-reviewed Journal of the American Medical Association.

Generally, the papers reported the story accurately. It is always difficult to justify the use of a "miracle" cure, because it means different things to different people – and the improvements cited for some people do seem worthy of the tag. However, while the treatment looks promising, it's at an early stage of development. The treatment is very aggressive, and also tested in specific types of MS, so may not be suitable for all people with MS. Similarly, the treatment has not yet been proven effective or safe in large enough groups for the results to be reliable.

We have not been able to independently assess if the truth of the claims that "wheelchair-bound" MS patients who were treated in this way are now able to dance.

What kind of research was this?

This was a case-series testing a new stem cell treatment in people with relapsing-remitting MS or secondary progressive MS.

Most people in the study had relapsing-remitting MS, which tends to have distinct attacks of symptoms, which then fade away either partially or completely. Around 85% of people initially diagnosed with MS will have relapsing-remitting MS, according to the MS Society. Of those, around 65% will develop secondary progressive MS; typically 15 years after being diagnosed.

Secondary progressive MS is where there is a sustained build-up of disability that no longer fades away.

And the research also included a smaller group of people with secondary progressive MS. There is no cure for MS, but many different treatments are available to help with symptoms.

Case series are useful to test new treatments, but they have several limitations, meaning they can't prove the treatments are effective very accurately or reliably. The big downside is a lack of a comparison group, called a control group. This means that you never know how much better or worse the new treatment is compared with an existing treatment, or doing nothing. This limitation applies to this study.

What did the research involve?

The study gave 123 patients with relapsing-remitting MS and 28 with secondary progressive MS a stem cell transplant. The transplants were carried out at a single US institution between 2003 and 2014, and researchers followed the patients for up to five years to see how they did.

The average age of participants was 36 (ranging from 18 to 60) and most were women (85%). The average follow-up after treatment was 2.5 years.

The new treatment used chemotherapy drugs cyclophosphamide and alemtuzumab or cyclophosphamide and thymoglobulin, followed by infusion of stem cells isolated from the patients' blood.

Before treatment, participants were subjected to a range of questionnaires and assessments to rate their symptoms, level of disability and quality of life. These were repeated at regular intervals after to measure any changes.

The main measure of interest was an improvement in score of 1.0 or more on the Expanded Disability Status Scale (EDSS). The EDSS is a way of quantifying disability in MS and monitoring changes over time. It is widely used in clinical trials and in the assessment of people with MS.

The main analysis compared EDSS ratings before and after treatment, looking for statistically significant improvements. Similar comparisons were done for other measures of MS-related disability and quality of life.

What were the basic results?

Change in disability scores

There was significant improvement in disability up to four years after treatment. Reductions in the EDSS (disability) score of 1.0 or more were seen in half of patients at two years (50%, 95% confidence interval (CI) 39% to 61%) and almost two out of every three people at four years (64%, 95% CI 46% to 79%).

Scores from the EDSS improved significantly. Before treatment, the average (median) EDSS score was 4.0, which improved to 3.0 at two years and to 2.5 at four years. Both were statistically significant reductions.

Taking the reduction of 4.0 to 2.5, this means the person went from having "Significant disability, but self-sufficient and up and about some 12 hours a day. Able to walk without aid or rest for 500m" to "Mild disability in one functional system or minimal disability in two functional systems".

However, some people did not improve. The EDSS score did not improve in people with secondary progressive MS or in those with disease duration longer than 10 years.

Ratings of disability and quality of life

Many other measures also improved, including neurological function, walking function, hand function and self-reported quality of life. The tests also involved a brain scan assessing the size of inflammation at a specific part of the spinal cord in the upper back (the T2 vertebra), which is said to correlate with disease severity. After treatment, the size of the damage reduced, and stayed lower up to two years longer.

Improvements quoted in the news

Some of the more miraculous findings were reported in the news, but not in the study publication itself. The Telegraph, for example, reported: "Patients who have been wheelchair-bound for 10 years have regained the use of their legs … while others who were blind can now see again."

We couldn't confirm these biblical results, based on the publication alone. They may have come from interviews with the study team or case studies provided by the research institutions.

How did the researchers interpret the results?

The researchers summed up that: "Among patients with relapsing-remitting MS, nonmyeloablative hematopoietic stem cell transplantation was associated with improvement in neurological disability and other clinical outcomes."

To their knowledge: "this [was] the first report of significant and sustained improvement in the EDSS score following any treatment for MS".

Conclusion

This case-series showed that a new stem cell treatment reduced the disability in people with relapsing-remitting MS up to four years after treatment. It worked in more than half of those given treatment. The authors claim that this was the first time this had been achieved, and is important because there is currently no cure for MS.

Given the relative lack of alternative treatments for MS, these results are encouraging. However, there are issues to bear in mind.

The average EDSS score before treatment in the group was 4.0. The scale goes from 10 (death due to MS), to 1.0 (no disability). Ratings above 5.0 involve impairment with walking. An average of 4.0 suggests most people didn't have the more severe forms of MS. A small number of people with more severe MS were included in the study, but too few to reach any reliable conclusions about this subgroup. Therefore, the results are most applicable to those with non-severe relapsing-remitting MS.

The treatment only improved the main outcome (EDSS improvement of 1.0 or more) in 50% of people after two years, meaning it didn't work in the other half. It worked for slightly more people after four years. It also didn't work in people with MS over 10 years or those with secondary progressive MS. This suggests that selecting the most appropriate patient group for this treatment will be important. It doesn't look like it would work for everyone.

These preliminary findings are from an uncontrolled study. This means we don't know if, or how much, the new treatment is better than any existing treatment, or doing nothing. The treatment was described by a study author in the Telegraph as being very aggressive, and only suitable for people who were fit enough to withstand the effects of chemotherapy. Chemotherapy is not without risk. Further studies will need to pay careful attention to weighing up the benefits and risks of this therapy.

Dr Sorrel Bickley, from the MS Society, cautiously welcomed the results in the Telegraph, saying: "Momentum in this area of research is building rapidly and we're eagerly awaiting the results of larger, randomised trials and longer-term follow-up data.

"New treatments for MS are urgently needed, but as yet there are no stem cell therapies licensed for MS anywhere in the world. This means they aren't yet established as being both safe and effective. This type of stem cell therapy is very aggressive and does carry significant risks, so we would strongly urge caution in seeking this treatment outside of a properly regulated clinical trial."