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AUTOLOGOUS MESENCHYMAL STEM CELLS FOR THE TREATMENT OF SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS: AN OPEN–LABEL PHASE 2A PROOF–OF–CONCEPT STUDY
  1. Peter Connick,
  2. Siddharthan Chandran
  1. University of Edinburgh

    Abstract

    Background Multiple Sclerosis affects over 2.1 million people worldwide,1 with over half of the prevalent population characterised by progressive forms of disease that result in the steady accumulation of fixed disability.2 The absence of treatments for progressive MS therefore represents a major unmet clinical need.3 Based on increasing experimental evidence that mesenchymal stem cells (MSCs) have biological properties of potential therapeutic relevance,4 and beneficial effects across a range of disease models,5 we assessed the safety and efficacy of autologous MSCs as a potential neuroprotective therapy for secondary progressive MS.6

    Methods Ten patients with secondary progressive MS involving the visual pathways (EDSS 5.5 to 6.5), received intravenous infusion of autologous bone marrow–derived MSCs derived using the European Group for Blood and Marrow Transplantation ex–vivo expansion procedures in a prospective open label phase IIA proof of concept study, registered at ClinicalTrials.gov NCT00395200. Adverse events were compared between pre–treatment and post–treatment periods of up to 20 and 10 months respectively. Using the anterior visual pathway as a model of wider disease, efficacy outcomes were also chosen to assess change at the point of treatment in functional, structural, and physiological measures. Blinded endpoint analyses were used for electrophysiological and selected imaging outcomes.

    Results MSCs were successfully isolated, expanded, characterised, and administered in all patients. The mean dose was 1·6×106 cells (min–max range 1·1–2·0) per kg bodyweight. One patient developed a transient rash not requiring treatment shortly after treatment; and two patients had self–limiting bacterial infections 3–4 weeks after treatment. No serious adverse events were observed. Improvement following treatment was seen in visual acuity and VER latency (difference in monthly rates of change: –0·02 LogMAR units [95% CI –0·03 to –0·01], p=0·003); and –1·33 ms [95% CI –2·44 to –0·21], p=0.020), with an increase in optic nerve area (difference in monthly rates of change 0·13 mm2 [95% CI 0·04 to 0·22], p=0·006). Exploratory analysis for non–linear effects showed cessation of treatment effects approximately six months after intravenous infusion.

    Conclusions Autologous MSCs can be safely administered in secondary progressive MS with evidence to suggest structural, functional and physiological improvement following treatment consistent with neuroprotection. The transient treatment response seen implied a likely requirement for repeat infusions to sustain benefit in the long–term.

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