Transplanting mesenchymal stem cells (MSCs) is safe and can delay disease progression in people with active, progressive multiple sclerosis (MS), according to results from a single-center clinical trial conducted in Israel.

Six months after the transplant, a considerable proportion of patients showed no signs of disease activity, compared to placebo treatment.

The findings were shared at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held Sept. 11–13 in Stockholm.

Dimitrios Karussios, MD, PhD, a neurologist at Israel’s Hadassah University Hospital, presented the trial’s results in a talk titled “ Indications of neuroprotective effects in progressive multiple sclerosis following autologous mesenchymal stem cells (MSC) transplantation: report of a randomised phase IIb double blind trial. “

Recent studies have raised hope for adult stem cell therapy as an MS treatment to slow disease progression and help repair damage to the nervous system.

A great deal of interest has been shown in transplanting hematopoietic stem cells (HSCs), but some lines of research also are exploring the use of MSCs — adult stem cells found in several parts of the body, including the bone marrow, skin, and fat tissue.

An MSC transplant (MSCT) involves collecting a patient’s MSCs from the bone marrow or blood, and expanding their numbers in the lab. Cells are then infused back into the patient’s blood (intravenous injection), or the fluid surrounding the spinal cord (intrathecal injection).

MSCs have been studied for their benefits in neurodegenerative diseases due to their ability to reduce inflammation, to make the immune system less active, and for their capacity to enhance neuronal repair, including myelin repair. (Myelin is the protective coat surrounding neurons, which is destroyed in MS.)

A few clinical studies suggest that MSC transplant is safe for people with MS and amyotrophic lateral sclerosis (ALS).

Now, researchers report the results of a Phase 2 clinical trial (NCT02166021) assessing the safety and effectiveness of two protocols of MSC transplant in people with active, progressive MS.

This trial was conducted at Hadassah University Hospital, and enrolled 48 patients with progressive MS (age 65 or younger), and moderate-to-severe disability (EDSS ranging from 3.0 to 6.5). All had failed to respond to at least one line of MS therapy.

Patients were divided randomly into three groups, each receiving mesenchymal stem cells either by intrathecal injection (IT) or intravenous injection (IV), or a placebo injection. After six months, treatment groups crossed over, and patients were again given either an MSC transplant or a placebo. Of note, MSCs were collected from patients’ bone marrow.

During the study and at its end, participants were monitored for changes in physical and neurocognitive abilities using several measures or tools, including magnetic resonance imaging (MRI) scans. An eye examination was included to detect loss of vision from optic nerve damage, a common symptom of MS.

Effectiveness was determined primarily by measures of treatment failure in patients, the study’s primary goal.

Data covering two cycles of six months were pooled to provide a single measurement for each group.

Results showed that significantly fewer transplanted patients experienced a treatment failure, which was determined as either an increase in EDSS or deterioration in any functional system seen using this scale relative to the study’s start.

Specifically, the proportion of patients who experienced a disability worsening was 6.7% in the MSC-IT group, 9.7% in the MSC-IV group, and 48.4% in the placebo group.

Importantly, 58.6% of the patients given an intrathecal injection transplant, and 40.6% of those given MSC by intravenous injections reached no evidence of disease activity (NEDA, a measure that refers to a state with no relapses, no EDSS progression, and no new or active lesions on MRI), compared with 9.7% in the placebo group.

Comparing the two forms of MSCs delivery, greater benefits were observed when MSCs were given by IT, reflected in better monthly changes in MRI lesion burden, physical and cognitive ability, and retinal nerve fiber damage.

The treatment seemed safe, and “no serious treatment-related adverse events were observed,” Karussios said.

The most common side effect was headache, but it was similar among all groups. As such, it was considered most likely to be related to the procedure itself, and not to the treatment.

Overall, “intravenous and intrathecal administration of autologous BM [bone marrow]-MSCs was safe,” and “induced beneficial clinical effects as compared to placebo treatment in all primary clinical endpoints (EDSS changes),” Karussios said.

Concerning the delivery procedure used for MSCs, “intrathecal treatment was superior to intravenous,” Karussios said, and “a repeated injection [six months later] induced additional benefits.”

The researcher emphasized that a Phase 3 clinical trial is warranted to confirm these findings.