Mesenchymal Stem Cell Transplant With NG-01 Treatment Shows Promise in Progressive MS

Treatment with NG-01 — an approach that uses patients’ own mesenchymal stem cells (MSCs) — safely and effectively delayed disease progression in people with active, progressive multiple sclerosis (MS), according to final data from a Phase 2 clinical trial.

Delivering these cells directly into the cerebrospinal fluid (CSF) — the fluid that bathes the brain and spinal cord — resulted in greater benefits in all evaluated disease measures, than when cells were injected into the bloodstream.

Initially created by researchers at Israel’s Hadassah Medical Center, NG-01 is being further developed by NeuroGenesis, following a license from Hadasit, Hadassah’s Technology Transfer Company.

“The treatment was well tolerated and the trial met all of its primary [goals],” Dimitrios Karussis, MD, PhD, the trial’s principal investigator and the director of Hadassah’s MS Center, said in a press release.

“The patients’ improvement was in many cases quite remarkable and included regain of motor function and noticeable effects on their cognitive abilities,” Karussis said.

Tal Gilat, NeuroGenesis’ CEO, said they are “extremely pleased to witness the significant positive effect of our NG-01 cells” in a “chronic, debilitating disease with no satisfactory treatment to improve or reverse established disability.”

The results were reported in the study, “Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis,” published in the journal Brain.

These promising findings — already shared with the U.S. Food and Drug Administration — are planned for further validation in a larger Phase 3 trial.

NG-01 involves collecting a patient’s bone marrow to expand a unique, proprietary subpopulation of MSCs with high immunosuppressive potential, neuroprotective properties, and regenerative capabilities.

These cells then are returned to the patient, where they are expected to travel to injury sites in the central nervous system (brain and spinal cord) and prevent further damage or even help repair current damage.

Conducted at Hadassah Medical Center, the Phase 2 clinical trial (NCT02166021) evaluated the safety and effectiveness of NG-01 — given through two different administration routes — against a placebo in 48 adults (27 men and 21 women), up to age 65 who have active, progressive MS.

Study participants — 41 with secondary progressive MS and seven with primary progressive disease — had a mean age of 47.6, a mean disease duration of 12.7 years, and moderate-to-severe disability. They also had failed to respond to at least one line of MS therapy.

Participants were assigned randomly to one of three groups, with 16 patients each.

Patients in the first group received NG-01 directly into the bloodstream and a placebo (sham) injection into the CSF (intravenous group); those in the second group were given NG-01 directly into the CSF plus a sham injection into the bloodstream (intrathecal group). The third group received two sham injections — one into the bloodstream and the other into the CSF (placebo group).

After six months, half of the patients in the first two groups received another NG-01 injection, while the other half was given a sham injection, and all placebo group participants were given NG-01 — half into the bloodstream and the other half into the CSF.

The trial’s main goals were to assess the occurrence of adverse events (side effects) and the proportion of patients in whom treatment failed — determined by an increase in the EDSS disability score or the Functional Systems Scores (FSS), at six and 12 months (the end of each treatment cycle).

Secondary goals included assessing changes in patients’ relapse rates, brain lesions, brain volume, brain motor networks, walking abilities, hand dexterity, cognitive function, and eye damage. Data covering two treatment cycles of six months were pooled to provide a single measurement for each group.

Results showed that treatment failure was significantly more frequent in the placebo group than in the other two groups. Specifically, about five times more patients in the placebo group showed disability worsening in the EDSS (41.9% vs. 6.7–9.7%) and twice as many had deterioration in the FSS (76.7% vs. 27.6–31%).

During both treatment cycles, the mean EDSS score increased in the placebo group (indicating disability worsening) and dropped in both NG-01 groups. Notably, two patients in the intrathecal group and three in the intravenous group showed disability improvements already during the first treatment cycle, and these numbers rose between twofold to fivefold during the second cycle.

In addition, significantly more patients in the NG-01 groups showed no evidence of disease activity (NEDA) during the entire study — 58.6% in the intrathecal group and 40.6% in the intravenous group, as opposed to 9.7% in the placebo group. NEDA is a state defined by the absence of relapses, EDSS progression, and new or active brain lesions.

Participants in both NG-01 groups also showed significant improvements in their walking abilities, compared with those in the placebo group.

Moreover, significant improvements in other key effectiveness goals, including relapse rate, brain lesions, hand dexterity, brain motor networks, cognitive function, and eye damage, were observed only among patients given NG-01 intrathecally, suggesting “a superiority of intrathecal over intravenous administration.”

Further analysis showed that a second intrathecal injection of NG-01 significantly boosted the effects observed during the first cycle of treatment. Similar, but less-pronounced, benefits were observed in the intravenous group.

“Overall, the robust effects of MSC transplantation on various parameters that reflect neurological dysfunction and especially on multiple sclerosis activity, may indicate the involvement of (central and peripheral) immunomodulatory and possibly also neuroprotective mechanisms,” the researchers wrote.

NG-01 was generally safe, with most adverse events being temporary or short-lasting and with no reports of treatment-related serious adverse events. The most common adverse events in all three groups were headache and back pain, which both were deemed to be related to the procedure itself, but not to treatment.

“These data may contribute to the design of future trials with cell therapies and the use of objective biomarkers for the evaluation of neurodegeneration and neuronal regeneration,” the team wrote, stressing that a Phase 3 trial is needed to confirm these findings.

NeuroGenesis also is working on the development of a similar therapy for other neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease.