A new study suggests that the injection, of a type of stem cell, into the brains of patients living with progressive multiple sclerosis is safe, well-tolerated, and has a long-lasting effect that appears to protect the brain from further damage. The findings are a step towards developing an advanced cell therapy treatment for progressive MS.

Currently, more than 2 million people live with MS worldwide. In MS, the body’s own immune system attacks and damages myelin, the protective sheath around nerve fibers, causing disruption to messages sent within the brain and spinal cord. While treatments exist that can reduce the severity and frequency of relapses, two-thirds of MS patients still transition into a secondary progressive phase of the disease within 25-30 years of diagnosis, where disability grows steadily worse.

Key immune cells involved in this process are macrophages, which ordinarily attack and rid the body of unwanted intruders. A particular type of macrophage known as a microglial cell is found throughout the brain and spinal cord. In progressive forms of MS, these cells attack the central nervous system, causing chronic inflammation and damage to nerve cells.

Recent advances have raised expectations that stem cell therapies might help ameliorate this damage. These involve the transplantation of stem cells, which can be programmed to develop into almost any type of cell within the body.

Previous work from Cambridge University researchers has shown in mice that skin cells reprogrammed into brain stem cells and then transplanted into the central nervous system, can help reduce inflammation and may be able to help repair damage caused by MS.

Now, scientists have completed a first-in-man, early-stage clinical trial that involved injecting neural stem cells directly into the brains of 15 patients with secondary MS recruited from two hospitals in Italy. The trial was conducted by teams at the University of Cambridge; Milan Bicocca, and the Hospitals Casa Sollievo della Sofferenza and S. Maria Terni, in Italy; Ente Ospedaliero Cantonale, in Lugano, Switzerland; and the University of Colorado.

The stem cells were derived from brain tissue from a single, miscarried fetal donor. The team followed the patients more than 12 months, during which time they observed no treatment-related deaths or serious adverse events. While some side-effects were observed, all were either temporary or reversible.

All the patients showed high levels of disability at the start of the trial – most required a wheelchair, for example. During the 12 month follow-up period, none showed any increase in disability or a worsening of symptoms. None of the patients reported symptoms that suggested a relapse, nor did their cognitive function worsen significantly during the study. Overall, researchers said, this points to a substantial stability of the disease, without signs of progression, though the high levels of disability at the start of the trial make this difficult to confirm.

The researchers assessed a subgroup of patients for changes in the volume of brain tissue linked to disease progression. They found the larger the dose of injected stem cells, the smaller the reduction in this brain volume over time. They speculate this may be because the stem cell transplant dampened inflammation.

The team also looked for signs that the stem cells were protecting nerve cells from further damage. Their previous work showed how tweaking the metabolism – how the body produces energy – can in turn reprogram microglia from ‘bad’ to ‘good.’ In this new study, they looked at how the brain's metabolism changes after the treatment. They measured changes in the fluid around the brain and in the blood over time, and found certain signs that are linked to how the brain processes fatty acids. These signs were connected to how well the treatment works and how the disease develops. The higher the dose of stem cells, the greater the levels of fatty acids, which also persisted during the 12-month period.

Researchers at the University of Cambridge said they recognize their study has limitations – it was only a small study and there may have been confounding effects from the immunosuppressant drugs, for example – but the fact that the treatment was safe and its effects lasted more than the 12 months of the trial means they can proceed to the next stage of clinical trials.

According to Dr. Ben Thrower, MS Focus senior medical advisor, “Any research looking at treatment options for SPMS or focusing on potentially reversing disability is welcomed and needed. The results of this trial should be met with cautious excitement. As the researchers stated, the trial was small and there was no control group. Is it possible that the stabilization of progression of disability in these patients was unrelated to the injected stem cells? Could any treatment effect have been the result of the tacrolimus immunosuppressant that all subjects were on for six months after treatment? Hopefully, future studies will answer these questions and show further positive results.”

The research was published in the journal Cell Stem Cell.