MS Speaks

Another Cell Therapy for MS Proves Safety


By John Gever, Managing Editor, MedPage Today

BOSTON -- A closely watched phase I trial of autologous mesenchymal stem cells (MSCs) for multiple sclerosis proved that the treatment was safe, with some hints that it might have helped some patients on the efficacy side, a researcher said here.

Aside from some mild infusion reactions, no adverse effects were seen in 24 patients who received intravenous infusions of autologous MSCs, said Jeffrey Cohen, MD, of the Cleveland Clinic.

With 6 months of follow-up, some patients showed "enticing" improvements on some exploratory efficacy measures, although there was no significant benefit seen for any measure across the entire group, Cohen told attendees at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting, held jointly this year with its North American counterpart.

Session co-moderator Neil Scolding, PhD, of the University of Bristol in England, told MedPage Today that these results are enough to warrant additional trials of this approach to MS.

"It's showing that [MSC therapy] is feasible, it's showing that it's safe and not producing side effects, and it hit those [safety] endpoints," he said, noting that earlier pilot trials had yielded similar results. Now, he added, controlled trials to test efficacy can get underway.

MSCs are an attractive candidate for cell-based therapy aimed at stopping and reversing the myelin loss in MS, which is ultimately responsible for the progressive disability seen in most patients over time. Autologous MSCs can be extracted from bone marrow which, while not fun for patients, is an established procedure that can be performed in many institutions. Their behavior in vivo and methods for expanding them ex vivo are also well known.

Studies in animals have shown that MSCs can, under the right conditions, mature into myelin-producing cells that counter myelin loss in MS disease models.

Although MSC-based therapies have been tested previously in a number of conditions with favorable safety results, Cohen said it was important that this phase I study look again at potential adverse effects, ranging from embolic phenomena and cardiac anomalies to tumor and ectopic tissue formation. MS exacerbation was also envisioned as possible, he said.

The phase I study enrolled 25 patients, of whom 24 were treated (sufficient MSCs could not be cultured ex vivo for re-infusion in one patient). Fourteen had secondary progressive MS and 10 had the relapsing-remitting form. Scores on the Expanded Disability Status Scale (EDSS) ranged from 3 to 6.5 (mean 5.2, median 6.0). Mean disease duration was 13.8 years (SD 9). The average patient age was 47.

A bone marrow aspiration was performed at enrollment and patients were then observed for 2 months, while the MSCs extracted were expanded ex vivo to a target of 2 million cells per kg of body weight. At the end of this period, patients received a single IV infusion of cells. Most patients received the target dose.

Besides the safety endpoints, the investigators tracked several efficacy outcomes, including change in EDSS and in MS Functional Scale scores, relapses, vision, retinal integrity, MRI lesion burden, and whole brain and gray matter atrophy rates.

Cohen said there were no treatment-related adverse effects of any kind rated as serious or severe. Infusion reactions were "minimal" and no evidence of MS disease activation or autoimmune activity was seen.

A "few" patients showed improvement in EDSS scores and in certain other of the efficacy measures. But overall, there was no significant change in any of these measures. Cohen noted that the study was not powered to detect clinical benefit.

Asked during the question period following his presentation what he would do differently if he could redesign the trial, he said he would probably use fresher MSCs and would increase the dose given back to patients.

Scolding told MedPage Today that there are still many unknowns about how best to deliver cell-based therapies in MS -- such as the route of administration, ex vivo manipulations, and dosing levels and intervals. That these early studies don't show dramatic clinical benefits is not a problem, he insisted.

"We are right at the very beginning of translation into clinical work, and we've got to get these safety data before we can move on to the larger studies, he said.

The study was funded primarily by the Dept. of Defense and the National Institutes of Health, with support from private foundations and other nonprofit entities.

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Cohen reported relationships with EMD Serono, Genentech, Innate Immunotherapeutics, Novartis, Vaccinex, Genzyme, Receptos, Synthon, and Teva.