Stem Cell Therapy Promising in Progressive MS

Megan Brooks

January 31, 2012

January 31, 2012 — Results of a small proof-of-concept study hint that autologous mesenchymal stem cells may have neuroprotective effects in multiple sclerosis (MS).

The study involved 10 patients with secondary progressive MS and objective evidence of optic nerve involvement resulting from demyelination. Over the course of 6 to 10 months after a single infusion of autologous mesenchymal stem cells in the central nervous system (CNS), researchers saw evidence of functional, neurophysiological, and structural improvement in vision without evidence of significant adverse effects.

The patients also experienced a reduction in functional disability, as measured by the Expanded Disability Status Score (EDSS).

Peter Connick, MRCP, from the Department of Neurosciences, University of Cambridge, United Kingdom, and colleagues reported the results in an article published online January 10 in Lancet Neurology.

"The signs of repair measured in most of the patients...raise substantial interest," Mark S. Freedman, MD, from the University of Ottawa Neurology Program in Ontario, Canada, and Antonio Uccelli, MD, from the Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Italy, write in a linked comment.

Major Unmet Clinical Need

Despite major advances in immunomodulatory therapies for patients with relapsing-remitting MS, there are no proven or available treatments to slow, stop, or reverse the accumulation of fixed disability characteristic of secondary progressive MS, the study team notes. The absence of treatments for this type of MS, which affects more than half of the patient population is a "major unmet clinical need," they write.

Their study grew out of preliminary evidence suggesting that mesenchymal stem cells have a beneficial effect in acute and chronic animal models of MS.

The investigators isolated, expanded, and characterized autologous bone marrow–derived mesenchymal stem cells from 10 patients with secondary progressive MS who had clear and objective evidence of optic nerve involvement, and then readministered them. None of the patients had received interferon-beta or glatiramer acetate within 6 months of entering the trial, or had previously used other disease-modifying therapies at any point.

The primary objective was to assess feasibility and safety. The investigators report that 1 patient developed a transient rash shortly after treatment, and 2 had self-limiting bacterial infections 3 to 4 weeks after treatment, but there were no serious adverse events.

As a secondary objective, they assessed the effect of treatment on the anterior visual pathway "as a model of wider disease," they explain.

After treatment, there was evidence of significant improvement in visual acuity and visual-evoked response latency, and an increase in optic nerve area.

Table. Noteworthy Visual Efficacy Outcomes

Visual Measure Rate of Change (95% Confidence Interval) P
Acuity (logMAR units) −0.2 (−0.03 to −0.01) .003
Evoked response latency (ms) −1.33 (−2.44 to −0.21) .020
Optic nerve area (mm2) 0.13 (0.04 - 0.22) .006

MAR = minimum angle of resolution

In their comment, Dr. Freedman and Dr. Uccelli say the improvement seen in the anterior visual pathway "might be an indicator of a more general process within the CNS," which is suggested by the reduction in functional disability on the EDSS. The "large, but statistically non-significant, changes in T1 lesion volume and magnetisation transfer ratio" also support this possibility, they note.

However, many visual measures did not show statistically significant changes after treatment, including color vision, visual fields, macular volume, retinal nerve fiber layer thickness, or optic nerve magnetization transfer ratio. "Particularly disappointing," Dr. Freedman and Dr. Uccelli say, were the results for optical coherence tomography, "which we all hoped might be a sensitive index for repair."

More Study Needed

Exactly how autologous mesenchymal stem cell therapy might exert a beneficial effect remains to be determined. However, the increase in optic nerve area and reduction in visual-evoked response latency are "consistent with a neuroprotective effect," Dr. Connick and colleagues write.

Katerina Akassoglou, PhD, from the Gladstone Institute of Neurological Disease and the Department of Neurology, University of California, San Francisco, who was not involved in the study, told Medscape Medical News, "It could be that mesenchymal stem cells have a direct protective effect or their role could be more indirect (perhaps) enhancing repair by suppressing inflammatory processes. At this point, I don't think there is a clear answer as to why the mesenchymal stem cells work in the context of neuroinflammation."

Dr. Akassoglou said this study is "an interesting starting point for future studies of mesenchymal stem cells in MS." She noted that the study included only 10 patients, and that "it needs to be followed-up with a larger number of patients, and also longer follow-up to test for potential adverse effects and see if the improvement in optic nerve pathology and general neurologic deficits that they observed is sustained," Dr. Akassoglou said.

Funding for the study was provided by the Medical Research Council, Multiple Sclerosis Society of Great Britain and Northern Ireland, Evelyn Trust, National Health Service National Institute for Health Research, Cambridge, United Kingdom, and the University College London Hospitals Biomedical Research Centres, Wellcome Trust, Raymond and Beverly Sackler Foundation, and Sir David and Isobel Walker Trust. Dr. Freedman and Dr. Uccelli have created the International Mesenchymal Stem Cell Transplantation Study Group, for which they receive no personal funding. The study authors and Dr Akassoglou have disclosed no relevant financial relationships.


Lancet Neurol. Published online January 10, 2012. Abstract, Editorial


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