Research: Early UK Stem cell Trials


Connick P et al. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol. 2012 Jan 9. [Epub ahead of print]

BACKGROUND:More than half of patients with multiple sclerosis have progressive disease characterised by accumulating disability. The absence of treatments for progressive multiple sclerosis represents a major unmet clinical need. On the basis of evidence that mesenchymal stem cells have a beneficial effect in acute and chronic animal models of multiple sclerosis, we aimed to assess the safety and efficacy of these cells as a potential neuroprotective treatment for secondary progressive multiple sclerosis.

METHODS:Patients with secondary progressive multiple sclerosis involving the visual pathways (expanded disability status score 5·5-6·5) were recruited from the East Anglia and north London regions of the UK. Participants received intravenous infusion of autologous (the individual gets their own cells) bone-marrow-derived mesenchymal stem cells in this open-label (non-blinded to treatmet) study.

Our primary objective was to assess feasibility and safety; we compared adverse events from up to 20 months before treatment until up to 10 months after the infusion. As a secondary objective, we chose efficacy outcomes to assess the anterior visual pathway as a model of wider disease. Masked endpoint analyses was used for electrophysiological and selected imaging outcomes. This trial is registered with, number NCT00395200.

FINDINGS:We isolated, expanded, characterised, and administered mesenchymal stem cells in ten patients. The mean dose was 1·6 million cells per kg bodyweight (range 1·1-2·0). One patient developed a transient rash shortly after treatment; two patients had self-limiting bacterial infections 3-4 weeks after treatment. We did not identify any serious adverse events. We noted improvement after treatment in visual acuity (difference in monthly rates of change -0·02 logMAR units, 95% CI -0·03 to -0·01; p=0·003) and visual evoked response latency (-1·33 ms, -2·44 to -0·21; p=0·020), with an increase in optic nerve area (difference in monthly rates of change 0·13 mm(2), 0·04 to 0·22; p=0·006). We did not identify any significant effects on colour vision, visual fields, macular volume, retinal nerve fibre layer thickness, or optic nerve magnetisation transfer ratio.

INTERPRETATION:Autologous mesenchymal stem cells were safely given to patients with secondary progressive multiple sclerosis in our study. The evidence of structural, functional, and physiological improvement after treatment in some visual endpoints is suggestive of neuroprotection.

Mesenchymal stem cells (MSC) have the potential to become alot of things

The studies in animal models have so far shown that animal and human mesenchymal stem cells have benefit by inhibiting the inflammatory response rather than by becoming nerve cells and causing direct repair.

Most studies have show that simply inhibiting immune responses is not enough to really stop progressive MS. Therefore, it is of interest that there were apparent improvements in electrophysiological results, that suggest that remyelination could be occuring (although magnetisation transfer ratio, supposed to detect myelination was not affected). This study was really designed to show that this type of treatment was safe. It appears that this is the case. Further studies on mesenchymal stem cell transplation in MS are on the way.

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  • Hmm, could the benefits be down to a placebo effect? I'm sure I read on this blog that Mesenchymal Stem Cells and Marrow Stromal Cells have never really shown to have remyelination properties.

  • I mentioned at the end of post that the experimental evidence in animals has suggested that the major action so far seen, is as an immunomodulatory. (New trials about to start therefore will recruit gadolium enhancing RR or progressive MSers). However if they have no reperative potential then we may as well use gilenya, tysabri etc, etc.

    We want to see them do something else. Maybe this is what is being seen in this study. But it could be placebo but could be cell effect also. This is why the trials are being done. Maybe the results were not earth shattering yet, but this is all about safety. It is a first step. There will be more

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