Could Stem Cells Reduce Inflammatory Lesions in Patients With MS?

ORLANDO—An international group of researchers has begun to study whether mesenchymal stem cells (MSCs) could reduce inflammatory lesions in patients with multiple sclerosis (MS). Pilot clinical trials have demonstrated that MSCs are safe, but their patient populations have been too small to prove the treatment’s efficacy, according to a presentation given at the Fifth Cooperative Meeting of the Consortium of MS Centers (CMSC) and the Americas Committee for Treatment and Research in MS (ACTRIMS).

MSCs can be derived from bone marrow or placenta, said Mark Freedman, MD, Professor of Neurology at the University of Ottawa. Various anti-inflammatory models showed that the cells have immunologic properties, and they can release growth factors that might offer neuroprotection, he added. Human MSCs promoted the differentiation of myelin-expressing cells in a mouse model of experimental autoimmune encephalomyelitis.

An International Study of MSCs’ Efficacy
Dr. Freedman and Antonio Uccelli, MD, Associate Professor of Medical Sciences at the University of Genoa, led a group that established a consensus protocol for a clinical trial to test the efficacy of MSCs for patients with relapsing-remitting, secondary progressive, or primary progressive MS who continue to have active relapses or enhancing MRI lesions despite receiving treatment. Research groups in 12 countries will participate in the protocol, which was published in the April 2010 Multiple Sclerosis Journal. The investigators will aspirate bone marrow from each patient and culture MSCs from it. The researchers will create enough cells for the trial and additional cells that can be studied for their immunologic properties.

Patients will be randomized to sham treatment or to a standard IV dose of one to two million MSCs per kilogram. Participants in the treatment arm will receive MSCs cultured from their own bone marrow. The study’s primary outcomes are safety and the reduction in the number and volume of new enhancing lesions over six months. After six months, the investigators will administer MSCs to patients in the sham group. All patients will be followed for one year so that the researchers can examine the crossover effect in the patients who received delayed treatment.

In addition to efficacy, the investigators plan to study the endurance of MSCs’ effect over time and whether MSCs can promote CNS repair. Several exploratory outcome measures, such as effects on reparative signals on MRI, neurophysiology, cognition, or clinical capability “are key to deciding whether these cells are capable of doing the wonderful things that you’ve heard about,” said Dr. Freedman.

Pilot Studies Indicate That MSCs Are Safe
An “intriguing” proof-of-concept study published in the February 2012 Lancet Neurology suggested that MSCs could promote recovery in patients with secondary progressive MS and optic nerve lesions, said Dr. Freedman. The investigators gave 10 patients an IV infusion of approximately two million autologous MSCs per kilogram. The cells had been derived from the patients’ bone marrow and cultured with fetal bovine serum. During the 10-month follow-up, patients’ visual acuity and visual evoked response latency improved. In addition, the diameter of patients’ optic nerves increased. “There were trends on the general MRIs of the brain to having fewer T2 lesions and less atrophy,” added Dr. Freedman.

A recent case study also suggested a potential benefit of MSCs for patients with MS. Researchers in China preconditioned a patient with cyclophosphamide and subsequently administered 10 million MSCs intrathecally and 20 million MSCs IV. On day three, the patient had sensory impairment, but muscle strength increased by day nine. The patient’s neurologic signs improved by day 52, and the patient became mobile. The Expanded Disability Status Scale (EDSS) score decreased to 6.5, and the MRI showed improvement.

Results of other small studies have been less clear. Israeli researchers gave 15 patients with MS intrathecal and IV doses of autologous MSCs. Some of the patients in this study developed headache and fever, which were interpreted as side effects of intrathecal administration. Patients’ EDSS decreased slightly, but not significantly, from a mean of approximately 6.

In a phase 1 study, Iranian researchers gave infusions of MSCs to 10 patients with progressive MS and followed them for various periods of time. EDSS declined from 4.5 to 2.5 for some patients, but other patients got worse. At least six patients had continued attacks that required the administration of steroids. The treatment “certainly didn’t turn off the disease,” said Dr. Freedman.

“We’re all in agreement that these cells are easy to get and easy to culture,” he added. The current, large-scale study will provide more clarity about the therapeutic potential of MSCs.

—Erik Greb
Senior Associate Editor