A colleague recently sent me an article (Nash et al JAMA Neurol. Published online December 29, 2014) about early results from a study of the safety and effectiveness of stem cell transplantation in people with MS. She asked me what I thought and if I thought this was important for people with MS to know.
First and foremost, it is always important for people to know about research that is meaningful to them. Thus, this research related to stem cells in people with MS would be something that people with MS might want to know about. However, it is critical that people understand the research that was done and the implications – independent of the news headlines reporting it.
Stem cell research is not unique to MS. Since stem cells have the potential to develop into different cell types over the course of one’s lifetime, they also offer promise for treatment of various diseases, such as heart disease, stroke, Parkinson’s disease and diabetes. There is also research directed at repair after injury, such as spinal cord injury and burns. Although there is excitement surrounding stem cells as a potential to cure disease and injury, there is also a tremendous amount of research yet to be done to determine the best way to deliver stem cells, and whether or not they are safe and effective for people with MS, or any of the other diseases or injuries for which they are being used.
For this study, researchers used peripheral blood stem cells obtained from the person with MS them self (autologous). This treatment was combined with high dose prednisone before and after the stem cells were infused into the participant’s body in order to prevent relapse and fever. Chemotherapy was also provided daily before the stem cells were infused. The researchers are mainly interested in “time to treatment failure” during the first 5 years after treatment. This means that they are monitoring participants for disease activity or disability due to MS, such MS-related lesions in the brain or a relapse, or a change in function measured by a scale called the Kurtzke Expanded Disability Status Scale (EDSS).
One question that a person with MS should ask about this study is “who were the people in this study that received the stem cell therapy?” The participants in this study are between 18 and 60 years of age, with relapse remitting MS (RRMS) for less than 15 years. They had to have an EDSS score of 3.0 to 5.5 when enrolled into the study, which means that they could still walk but may were limited in some daily activities. Participants had to have failed disease modifying therapy, meaning that they had 2 or more clinically defined relapses during 18 months of therapy and an increase in the EDSS score that remained for 4 or more weeks.
So, the results of this study will most directly apply to people with these characteristics. Children and adolescents are not receiving the treatment; nor are people over 60 years of age. People with EDSS scores greater than 5.5, who present with more disability, also are not included. Thus, the findings of this study may not apply to children, adolescent or older adults, or those with greater disability. It is important to note that this is a Phase 2 clinical trial and therefore there is not a control group. Therefore, the outcomes in these participants are not compared to a group that did not receive the treatment. That makes it difficult to know if the treatment itself is what led to the changes that are reported. The researchers did try to adjust for this by taking measures at several time points, and also by comparing their data to that from other related studies.
What are the outcomes thus far? Does the infusion of these stem cells cure MS? Does it at least prevent relapse? The outcomes are more promising than an earlier study comparing a disease modifying therapy (natalizumab) to treatment with no disease modifying therapy. Specifically, in this study the survival rate (the rate of no relapse for a specific time) was estimated to be 82.8% at 2 years and 78.4% at 3 years, compared to 37% and 7%, respectively for the earlier study. An important note is that in the earlier study, the participants had a wider range of EDSS scores, from 0 to 5.0. The earlier study was conducted in people with less severe disability (lower EDSS scores), but the survival rate was higher (better) in this study with people who had greater disability (higher EDSS scores).
The paper also reports that unlike earlier studies of disease modifying therapies, participants in this study experienced improvements in function, and a decrease in disease activity, in the first 3 years. Function was measured with a functional outcome scale and the EDSS; disease activity was measured as the number of relapses and survival rate, and MRI (imaging of the brain). Participants also reported an improved quality of life. However, treatment was deemed to have failed in 2 participants after the first 3 years. The investigators will continue to follow the remaining participants through 5 years to confirm what they have already observed.
Another question someone should ask about results from a research study is whether or not there were adverse events, or any negative outcomes, in any of the participants. It is important to remember that this stem cell treatment is associated with significant risks. There were a number of adverse events reported, but most were what one would expect. Adverse events ranged from gastrointestinal disorders, and infections, to nervous system impairments, such as headaches, changes in sensation, and blurred vision. There were also reports of deep vein thrombosis, cardiac impairments, and pulmonary problems. Out of 24 participants, there were 2 participants who experienced an MS exacerbation, one of which died 2.5 years after treatment with stem cells.
The findings from this study are similar to those in another report of a case series in which people with MS were treated with immune-suppressing therapy followed by transplantation of blood stem cells (Burt et al. JAMA. 2015;313(3):275-284).In the 145 participants with RRMS followed for up to 5 years after treatment, EDSS scores improved in 50% (41 of 82) of the participants at year 2, and 64% (23 of 36) of participants at year 4. Disease activity was also reduced. The authors of that case series reported that people with secondary progressive MS and those with disease duration greater than 10 years did not demonstrate the same improvements
So, what do I think? I think that there are some promising findings, but that In order for any treatment to be considered as a reasonable option by people with MS, the effectiveness will need to outweigh the risks. Much research is required before deciding if treatment with these autologous stem cells is effective for halting the progression of disease activity and disability due to MS. This will require not only completion of this 5-year study, and comparison to other trials, but well-controlled clinical trials before we will know if the effectiveness is greater than the risk for people with MS.
Deborah Backus, PT, Phd
Director of Multiple Sclerosis Research
About Dr. Debbie
Deborah Backus, PT, PhD is Director of Multiple Sclerosis Research at the Shepherd Center in Atlanta, Georgia. Dr. Debbie received her B.S. in Physical Therapy in 1986, and her Ph.D. in neuroscience in 2004.