University of Cambridge scientist ‘cautiously excited’ about potential stem cell treatment for multiple sclerosis

A Cambridge professor is “cautiously very excited” about the results of a study into a potential stem cell treatment for multiple sclerosis.

An international team of scientists at the University of Cambridge, University of Milan Bicocca and Hospital Casa Sollievo della Sofferenza in Italy found injection of a type of stem cell into the brains of patients living with progressive MS is safe, well tolerated and has a long-lasting effect that appears to protect the brain from further damage.

More than two million people worldwide live with MS and while treatments can reduce the severity and frequency of relapses, two-thirds of patients still move into a debilitating secondary progressive phase of disease within 25 to 30 years of diagnosis, during which their disability grows steadily worse.

In MS, the body’s immune system attacks and damages myelin - a protective sheath around nerve fibres - which causes disruption to messages sent around the brain and spinal cord.

Macrophages - immune cells that ordinarily attack unwanted intruders - are key to this process. One type of macrophage, known as a microglial cell found in the brain and spinal cord, attacks the central nervous system (CNS) in progressive forms of MS, causing chronic inflammation and damage to nerve cells.

But there are hopes that transplanting stem cells - the body’s ‘master cells that can be programmed into any cell type in the body - could help counter the damage.

The Cambridge team previously showed that skin cells reprogrammed into brain stem cells and transplanted into the central nervous system of mice helped reduce inflammation and may help repair damage caused by MS.

Now the first in-human, early-stage clinical trial has been completed.

Neural stem cells were injected directly into the brains of 15 patients with secondary MS recruited from two hospitals in Italy.

The stem cells were derived from cells taken from brain tissue from a single, miscarried foetal donor.

The Italian team has previously shown a virtually limitless supply of these stem cells could be produced from a single donor and in future it may be possible to derive them directly from the patient, overcoming the practical problems associated with the use of allogeneic foetal tissue.

Over 12 months, the patients had no treatment-related deaths or serious adverse events and side-effects were temporary or reversible.

All the patients showed high levels of disability at the start of the trial, with most requiring a wheelchair, but a year later none showed any increase in disability or a worsening of symptoms.

None reported symptoms that suggested a relapse and their cognitive function did not worsen significantly during the study.

The researchers say 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.

A subgroup of the patients were assessed for changes in the volume of brain tissue associated with disease progression. The larger the dose of injected stem cells, the smaller the reduction in this brain volume over time, it was found, which the researchers speculate may be because the stem cell transplant dampened inflammation.

They also searched for signs that the stem cells were having a neuroprotective effect, meaning protecting nerve cells from further damage.

Earlier work showed how altering the metabolism can reprogramme microglia from ‘bad’ to ‘good’, so in the new study, they examined how the brain's metabolism changed after the treatment.

Measuring changes in the fluid around the brain and in the blood over time, they found signs linked to how the brain processes fatty acids. The higher the stem cells dose, the greater the levels of fatty acids.

Such signs are connected to how well the treatment works and how the disease develops.

Prof 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, which are a step towards developing a cell therapy for treating MS.

“We recognise that our 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 our treatment was safe and that its effects lasted over the 12 months of the trial means that we can proceed to the next stage of clinical trials.”

Co-leader Prof Angelo Vescovi, from the University of Milano-Bicocca, added: “It has taken nearly three decades to translate the discovery of brain stem cells into this experimental therapeutic treatment This study will add to the increasing excitement in this field and pave the way to broader efficacy studies, soon to come.”

Caitlin Astbury, research communications manager at the MS Society, says: “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.”

The research was published in Cell Stem Cell.