First Study of Neural Cells for Stroke Shows Promise

April 30, 2015

The first study of human neural stem cells delivered directly to the brain in patients with stroke has shown no major harmful cell-related effects over 2 to 4 years' follow-up, with a suggestion of slight improvements in patient functionality.

Presenting the phase 1 study at the inaugural European Stroke Organisation (ESO) Conference 2015, Keith Muir, MD, University of Glasgow, United Kingdom, concluded that there were "sustained small neurological and functional improvements in most participants post-procedure" and that a phase 2 trial is warranted.

"There were a few adverse events from the neurosurgical procedures and anesthesia in elderly people," Dr Muir told Medscape Medical News. "But in terms of efficacy, most patients improved. NIHSS [National Institutes of Health Stroke Scale] scores improved in almost all patients, with an average significant 2-point reduction over 2 years."

Dr Keith Muir

He cautioned that the improvements seen could not definitely be attributed to the cells, "but we selected patients a long time after stroke and usually these patients do not improve much."

An "Interesting Observation"

However, he added that the results could have been due to patients being involved in the study because they were feeling more motivated. "We don't really know what it means as few studies have been done in patients this long after stroke," he said. "Nobody expects to see an improvement 3 to 5 years later. The medical system has given up on these patients. So I would say these results are encouraging but we need to be cautious, so they should be seen as an interesting observation."

The cells used in this study were from an allogenic multipotent human neural stem cell line derived from a single 12-week human fetal cortex tissue sample. They are an "off the shelf" commercialized product in development by ReNeuron, which funded this study.

Dr Muir explained that the cells are "immortalized" by being treated with the c-myc growth factor gene, "which keeps them as stem cells in perpetuity." The gene is chemically controlled by 4OH tamoxifen, which, when withdrawn, allows differentiation into all neural cell lineages.

He pointed out that "by putting the cells directly into the brain, we know the dose and we are delivering directly to the area of damage." Rather than replacing dead brain cells, it is believed the cells act as "clever little factories which respond to the environment they find themselves in and produce cocktails of chemicals which damp down the immune system and increase the mobilization of stem cells," he said.

The current study, known as the Pilot Investigation of Stem Cells in Stroke (PISCES) trial, was an open-label, ascending-dose phase 1 study. The cells were injected directly into the putamen area of the brain. The investigators had planned to enroll three patients at each of four doses: 2, 5, 10, and 20 million cells. However, recruitment was concluded after 11 patients because of an enforced change of manufacturing site.

Patients were in the chronic phase of stroke, having had an ischemic stroke involving the basal ganglia or subcortical white matter 6 months to 5 years previously. They had limb weakness and significant disability but had to have capacity to consent for participation and for neurosurgery.

Results showed no cell-related adverse events after a follow-up of 2 to 4.5 years, although there were some adverse effects due to surgery and anesthesia. Efficacy results suggested a small improvement in functionality.

Table. Change in NIHSS and Barthel Scores After 2 Years

Stroke Scale Baseline 2 Years Change P Value
NIHSS 7 5 –2 .002
Barthel 12 14 2 .18


A follow-on phase 2 study is now underway in patients at an earlier time point (2 to 3 months after stroke), during which there may be a greater chance of showing greater efficacy.

The PISCES trial was funded by ReNeuron. Dr Muir has disclosed no relevant financial relationships.

European Stroke Organisation (ESO) Conference 2015. Abstract 415. Presented April 19, 2015.


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