In Active MS, stem cells (MSCs) fail to reduce brain inflammation.
According to the results of an international Phase 2 clinical trial, intravenous therapy with mesenchymal stem cells (MSCs) failed to significantly reduce brain inflammation or improve clinical symptoms in people with active multiple sclerosis (MS).
The intravenous treatment was well-tolerated, but did not show any of the “demonstrated neuroprotective and ‘tissue healing’ properties [seen] in other studies,” according to the researchers, who used magnetic resonance imaging (MRI) scans to measure the therapy’s efficacy.
Mark Freedman, MD, a professor of neurology at the University of Ottawa in Canada, who co-led the experiment in Canada, said they failed to prove, at least on the measurements of MRI, that MSCs were able to suppress inflammation.
While this data shows that MSCs had no therapeutic benefits in this patient population, they contrast with prior findings in active, progressing MS patients who received a specific subpopulation of MSCs injected directly into the spinal canal. Mesenchymal stem cell transplantation is safe and can help delay the progression of MS, according to research.
Additional Research Required
As a result, additional research is required, according to Freedman. The mechanism of distribution, the quantity of cells, and how often to administer them are all factors that are encouraging for future research, he explained.
The findings were reported in The Lancet Neurology in a research titled “Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis (MESEMS): a phase 2, randomized, double-blind crossover experiment”.
MSCs are found in various regions of the body, including the bone marrow, skin, and adipose tissue, and are capable of developing into a variety of cell types. MSCs are gaining popularity as a potential treatment method for a variety of illnesses due to their strong immunosuppressive, anti-inflammatory, neuroprotective, and regenerative capabilities.
MSC transplantation usually entails extracting these cells from a patient, multiplying them in the lab, and then putting them back into the person’s bloodstream (intravenous injection) or the fluid around the brain and spinal cord (intrathecal injection).
MSCs have been shown in animal experiments to enhance brain and tissue healing, impact the immune response, and reduce MS-like symptoms.
MESEMS Phase 2 Clinical Trial
In the MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) Phase 2 clinical trial, 144 persons with active relapsing-remitting MS or progressive MS were assessed for the safety, tolerability, and effectiveness of bone marrow-derived MSCs.
Recent relapses and/or evidence of MRI activity were used to identify active MS.
The participants were randomly allocated to receive either an intravenous injection of MSCs followed by a subsequent placebo injection (69 patients) or an initial placebo injection followed by an intravenous injection of MSCs (75 patients). The second injection was given in both cases at week 24, or roughly six months after the first.
The trial’s primary objectives were to evaluate the therapy’s safety as well as changes in the number of gadolinium-enhancing brain lesions, which signify active inflammation, after 24 weeks.
Changes in other MRI-based outcomes, the number of relapses, and disability progression (as measured by the expanded disability status scale (EDSS)) between the start of the research and 24 weeks, and then again between 24 and 48 weeks were secondary aims (about one year).
The patients were 39 years old on average, and 65 percent of them had relapsing-remitting MS. The remaining 23% had secondary progressive MS, and the remaining 12% had primary progressive MS.
The one-year trial failed to reach all efficacy criteria, with no statistically significant trends favoring MSCs over the placebo, according to the findings.
The mean annualized recurrence rate (AAR) among patients initially randomized to the placebo was nearly twice as high as those given MSCs (1.1 vs. 0.6) during the first six months, but this difference did not achieve statistical significance.
MSC treatment was generally safe and well-tolerated, with similar incidence of adverse events in the first six months (about 53%) and between 24 and 48 weeks, or the second six months, amongst the groups (59 percent ).
Infections and infestations were the most commonly reported adverse events over the entire research. Up to 8% of patients experienced serious side effects, all of which were determined to be unrelated to MSCs. During the research, no one died.
According to the researchers, while MSC therapy has been proven to be safe independent of the administration route, neither inflammatory brain lesions on MRIs nor clinical surrogate measures of efficacy have shown efficacy “in previous studies and in MESEMS.”
Beware of the Hype
Freedman said it’s critical to know that there’s a lot of hype about these cells, and that a lot of clinics are earning money by enticing patients and promising them the chance to profit from mesenchymal stem cell transplantation.
“A lot of caution needs to be given to going to these centers since it was very difficult to prove, even in a very well-done trial, that the benefit is that easy to see,” he said.
More Trials Needed
More research is needed, according to Freedman and the other scientists involved in this Phase 2 study, to see if MSCs can indeed slow disease progression.
“Whether these negative results are attributable to a true absence of therapeutic activity of MSCs in multiple sclerosis, to the different MS types of enrolled patients, or to technical and methodological flaws in the experimental approach is still uncertain,” the researchers said.
Given MSCs’ neuroprotective and reparative properties in preclinical MS models, as well as their ability to delay disease progression in active, progressive MS patients in a small Phase 2 trial (NCT02166021) larger studies should assess whether MSCs can repair tissue and whether they are a valuable option for progressive MS patients, the researchers concluded.
Future trials should investigate other routes of administration, MSC sources, doses, and treatment regimens, since all of these factors could still demonstrate whether MSCs might be an effective therapeutic option for persons with multiple sclerosis in the future.