Hopeful early results for stem cell implantation in chronic stroke
medwireNews: A first-in-man study of neural stem cell transplantation has found no safety issues and shows hints of efficacy in patients treated at least 6 months after an ischaemic stroke.
The Pilot Investigation of Stem Cells in Stroke (PISCES), which is reported in The Lancet, was a phase I dose-escalation study in 11 patients, aged a median of 68 years, who had a stroke a median of 32 months previously. They were moderately disabled, with median National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores of 7 and 3, respectively.
Keith Muir (University of Glasgow, UK) and colleagues recruited only men because the human neural stems cells used (CTX0E03) are modified to contain a tamoxifen analogue receptor to facilitate growth in culture.
“Future studies, however, will not be limited to men as we saw no preclinical evidence of in-vivo cell-cycle switching and the safety profile was good”, they say.
The men received between 2 million and 20 million cells and were followed up for 2 years, during which there were no immunological or stem cell-related adverse events. Most early events were related to the procedure and were as expected for stereotactic surgery; these included extradural and subdural haematoma and a minor bleed at the burr hole. One patient developed a right occipital infarct, attributed to suspension of antiplatelet treatment before surgery.
The researchers say they opted for stereotactic intracranial injection, into the ipsilateral putamen, because it “ensures that the intended cell dose is delivered adjacent to the ischaemic damage, replicating the conditions of animal studies, which is more likely than less invasive routes to yield proof of concept.”
Other adverse events included malignant melanoma, flare up of diverticulitis and haematemesis, all in patients previously judged to be at risk of these conditions.
Five patients underwent brain imaging 1 and 12 months after implantation. In four patients, 17 of 28 brain slices showed reduced fractional anisotropy, but nine slices had increases, implying improved white matter microstructural integrity. The fifth patient, who received the lowest stem cell dose, had reductions in all slices.
Of note, despite stable disability scores at baseline, patients showed improvements in NIHSS, Barthel Index and Ashworth arm and leg scores. By 12 months, four patients had improved by one grade on the mRS, although this fell to three by 24 months, with two patients worsening by one grade and seven remaining stable throughout.
“Whether attributable to cell implantation or to other factors, such as engagement with trial assessments and increased generic medical input, change in this population suggests that trials of interventions are worthwhile late after stroke, when recovery is not generally believed to be attainable”, say Muir et al.
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