Afferent Visual Pathway Assessment in an Exploratory Trial of Autologous Mesenchymal Stem Cells in Multiple Sclerosis

There is a considerable need for treatments in MS for preventing progressive neurological disability. Assessment of the afferent visual pathway shows potential in investigating new therapies in MS. Mesenchymal Stem Cells exhibit properties of potential therapeutic relevance in progressive MS. A phase I/IIA trial of adult autologous mesenchymal stem cells as a potential therapy for Multiple Sclerosis [MSCIMS] was designed as an open label, pre (up to 20 months) vs. post treatment (up to 10 months) (single intravenous administration of autologous bone marrow derived mesenchymal stem cells) comparison study in ten secondary progressive MS patients. Primary end points were adverse events and secondary end points were efficacy measures. All 10 patients had previous history of clinical optic neuritis: this was in order to enable longitudinal structural and functional assessments of the disease-affected afferent visual pathway. Piecewise linear mixed models were used to assess the change in gradients over time at the point of intervention. All 10 patients tolerated the trial assessments and intervention. No significant or serious adverse events were seen. Improvement after treatment was seen in visual acuity and visual evoked response latency, along with an increase in optic nerve cross-sectional area. The results suggest that autologous mesenchymal stem cells are safe and could possibly promote endogenous repair mechanisms such as remyelination, although a definitive conclusion of this cannot be made from this small study. While MSCIMS was a proof of concept study only, based on the encouraging experience derived from it, there would seem to be potential value in future, larger placebo controlled, double-blinded, randomised therapeutic phase IIb/III trials that could (i) more definitively investigate stem cells as a therapy and (ii) use the visual pathway disease model for investigating the efficacy of potential neuroprotective and reparative therapeutic agents.