The injection of a type of stem cell into the brains of patients living with progressive multiple sclerosis (MS) has a long-lasting effect that appears to protect the brain from further damage, new research has found.
The research, led by scientists at the University of Cambridge, University of Milan Bicocca and Hospital Casa Sollievo della Sofferenza (Italy), is a step towards an advanced cell therapy treatment for progressive MS.
Professor Stefano Pluchino Professor Stefano Pluchino from the University of Cambridge, who co-led the study, said: “We desperately need to develop new treatments for secondary progressive MS, and I am cautiously very excited about our findings [..]”
More than two million people live with MS worldwide.
And while available treatments can reduce the severity and frequency of relapses, two-thirds of MS patients will go on to experience a debilitating secondary progressive phase of the disease within 25-30 years of diagnosis.
In MS, the body’s own immune system attacks and damages myelin – the protective sheath around nerve fibres, causing disruption to messages sent around the brain and spinal cord.
Key immune cells involved in this process are macrophages, which normally attack and rid the body of unwanted intruders.
One particular type of macrophage known as a microglial cell is found throughout the brain and spinal cord.
In progressive forms of MS, they attack the central nervous system (CNS), causing chronic inflammation and damaging nerve cells.
Researchers hope that one day, stem cell therapies might help ameliorate this damage by being programmed to develop into almost any type of cell within the body.
Previous work from the Cambridge research team has shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, can help reduce inflammation and may be able to help repair damage caused by MS.
Now, researchers have completed a first-in-human, 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 stem cells were derived from cells extracted from brain tissue from a single, miscarried foetal donor.
The team at the University of Milano-Bicocca in Italy had previously shown that it would be possible to produce a virtually limitless supply of these stem cells from a single donor – and in future it may be possible to derive these cells directly from the patient – helping to overcome practical problems associated with the use of allogeneic foetal tissue.
The researchers followed the patients over 12 months, during which time they observed no treatment-related deaths or serious adverse events.
While the researchers observed some side-effects, all were either temporary or reversible.
All the patients showed high levels of disability at the start of the trial but 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 and nor did their cognitive function decline significantly during the study.
Overall 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 said.
The scientists assessed a subgroup of patients for changes in the volume of brain tissue associated with disease progression.
They found that a larger the dose of injected stem cells was associated with a smaller the reduction in this brain volume over time.
The researchers speculate that this may be because the stem cell transplant dampened inflammation.
The research team also looked for signs that the stem cells were having a neuroprotective effect.
Their previous research showed how tweaking metabolism – how the body produces energy – can in turn reprogram microglia from ‘bad’ to ‘good’.
In the new study, they looked at how the brain’s metabolism changes after the treatment.
The researchers 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.
The 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 over the 12-month duration.
Caitlin Astbury, Research Communications Manager at the MS Society, said: “This is a really exciting study which builds on previous research funded by us.
“These results show that special stem cells injected into the brain were safe and well-tolerated by people with secondary progressive MS.
“They also suggest this treatment approach might even stabilise disability progression.
“We’ve known for some time that this method has the potential to help protect the brain from progression in MS.
“This was a very small, early-stage study and we need further clinical trials to find out if this treatment has a beneficial effect on the condition.
“But this is an encouraging step towards a new way of treating some people with MS.”
