Intravenous Allogeneic Mesenchymal Stem Cells for Stroke

A new study conducted by Michael Levy and colleagues has found the intravenous injection of allogeneic mesenchymal stem cells to be both a safe and effective treatment option for post-stroke long term recovery.  

The randomized, placebo-controlled study, published by the University of California enrolled 36 subjects who had experienced an Ischemic stroke >6 months before the date of study enrollment.  The study criteria also required that patients have no substantial improvement in neurological or functional status for 2 months before study enrollment. 

The safety portion of the study was split into 2 parts, each increasing the cell dosage upon completion of previous findings.  The maximum dosage was 150 million mesenchymal stem cells, as per the studies part 1 findings of established safety with 1.5 million cells/kg of body weight.  The parent cell bank had been tested for quality control including; cell count, viability (are the cells alive), appearance and viruses.

According to Michael Levy and colleagues:

"The primary study endpoint was safety and tolerability, evaluated in all subjects who received any portion of an infusion, and determined by the incidence/severity of adverse events, clinically significant changes on laboratory and imaging tests, vital signs, and physical plus neurological examinations. Four secondary endpoints were scored serially to derive preliminary estimates of efficacy: National Institutes of Health Stroke Scale, Barthel Index (BI), Mini-Mental Status Exam, and Geriatric Depression Scale. For each, the change from baseline was evaluated using Wilcoxon signed-rank test, with primary analysis of preliminary efficacy being change from baseline to 6 months post-infusion, and analysis including all subjects who received an infusion except for one subject who failed to return after the day 10 visit for all visits (except for month 9 follow-up)." (1)

Study participant safety

Testing disclosed no safety concerns among participants.  There we no positive reactions to intradermal testing (allergy testing).  

There were no significant findings after follow up physical examinations and blood testing.  

Subject behavioral improvements

"Across all subjects, improvements were seen in National Institutes of Health Stroke Scale, BI, Mini-Mental Status Exam, and Geriatric Depression Scale scores at both the 6-month and the 12-month follow-up visits." (1)

These were all found to be statistically significant, changes in the Barthel score ( a scale used to measure performance in daily living activities) increased from 11.4% at baseline (pre-treatment) to 35.5% improvement at 12 months post-treatment. This study showed that Mesenchymal stem cells can be a safe treatment for stroke that is potentially associated with functional improvements.  

"Intravenous infusion of MSC was found to be safe in 36 patients who had chronic stroke with substantial functional deficits. Across 3 escalating doses, treatment-related adverse events were infrequent, mild, and transient. Serial assessments of exam, laboratory testing, electrocardiogram, and CT scans of chest/abdomen/pelvis disclosed no safety concerns, with limited subject dropout. These results are consistent with the overall excellent safety record that MSC has in clinical trials of human subjects across numerous non-cerebrovascular diagnoses 15, 24–27 and in stroke trials." (1)

Conclusion

This is the largest study to assess the effects of intravenous MSCs in patients with chronic stroke. What we found quite impressive with this study is that patients with chronic stroke typically show functional decline. However, the study found that patients treated with MSCs experienced functional improvement over the course of 12 months.  

These findings showed that even after 12 months post-treatment MSCs still had broad effects on brain function.

Levy and colleagues also state that paired with a functional restorative therapy approach these cognitive improvements could provide maximum benefit, as opposed to MSC infusion alone.

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References:

1. Levy, Michael L., et al. “Phase I/II Study of Safety and Preliminary Efficacy of Intravenous Allogeneic Mesenchymal Stem Cells in Chronic Stroke.” Stroke, vol. 50, no. 10, 2019, pp. 2835–2841., doi:10.1161/strokeaha.119.026318.