Treatment with Umbilical Cord Stem Cells Safe with Sustained Benefits for MS, Trial Shows

Image of GMP syringe prep lab at Stem Cell Institute clinic in Panama.

Stem cells being prepared for treatment.

March 20, 2018
Jose Marques Lopes, PhD
Link to Original Story at Multiple Sclerosis News Today

Treatment with umbilical cord [tissue-derived mesenchymal] stem cells was found to be safe and leads to sustained improvements in disability and brain lesions of multiple sclerosis (MS) patients, according to a clinical trial.

The study, “Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis,” was published in the Journal of Translational Medicine.

Although current treatments for MS are able to reduce the frequency of flare-ups and slow disease progression, they are not able to repair the damage to nerve cells or the myelin sheath, the protective layer around nerve fibers.

Mesenchymal stem cells (MSCs) are adult stem cells found in multiple tissues, such as umbilical cord, bone marrow, and fat. These cells are able to mature into bone, cartilage, muscle, and adipose tissue cells.

MSCs may inhibit immune-mediated alterations. In particular, MSCs derived from the umbilical cord have a high ability to grow and multiply, increase the production of growth factors, and possess superior therapeutic activity, compared with other MSCs.

Diverse clinical studies have shown that MSCs can safely treat certain immune and inflammatory conditions, including MS.

The research team had previously demonstrated that MSCs can also improve cognitive and motor function.

Recent results with placenta or umbilical cord MSCs showed few mild or moderate adverse events, as well improvements in patients’ level of disability.

Researchers at the Stem Cell Institute in Panama have now completed a one-year Phase 1/2 clinical study (NCT02034188) to test the effectiveness and safety of umbilical cord MSCs for the treatment of MS.

The trial included 20 MS patients with a mean age of 41 years, 60 percent of whom were women. Fifteen participants had relapsing-remitting MS, four had primary progressive MS, and one had secondary progressive MS. Patients’ disease duration was a mean of 7.7 years.

Participants received seven intravenous infusions of 20×106 umbilical cord MSCs over seven days. The treatment’s effectiveness was evaluated at the start, at one month, and at one year after treatment.

Assessments included evaluating brain lesions with magnetic resonance imaging (MRI) and disability based on the Kurtzke Expanded Disability Status Scale (EDSS), as well as validated MS tests for neurological function, hand function, mobility, and quality of life.

Patients did not report any serious adverse events. Most mild adverse events possibly related to treatment were headaches, which are common after MSC infusions, and fatigue, which is common in MS patients, the authors observed.

Improvements were most evident at one month after treatment, namely in the level of disability, nondominant hand function, and average walk time, as well as bladder, bowel, and sexual dysfunction. Patients also reported improved quality of life.

MRI scans at one year after treatment revealed inactive lesions in 15 of 18 evaluated patients. One patient showed almost complete elimination of lesions in the brain, which “is a particularly encouraging finding,” the researchers wrote.

At the one year point, improvements in disability levels were also still present, and could translate into improved ability to walk and work without assistance.

“The potential durable benefit of UCMSC [umbilical cord MSC] at 1 month, and sustained in some measures to 1 year, is in stark contrast to current MS drug therapies, which are required to be taken daily or weekly,” the researchers wrote.

The safety of the treatment is another advantage over available MS therapies, the team said.

They concluded that “treatment with UCMSC intravenous infusions for subjects with MS is safe, and potential therapeutic benefits should be further investigated.”

Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study

Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, Du MQ, Luan SL, Altmann DR, Thompson AJ, Compston A, Scott MA, Miller DH, Chandran S.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Abstract

BACKGROUND:
More than half of patients with multiple sclerosis have progressive disease characterised by accumulating disability. The absence of treatments for progressive multiple sclerosis represents a major unmet clinical need. On the basis of evidence that mesenchymal stem cells have a beneficial effect in acute and chronic animal models of multiple sclerosis, we aimed to assess the safety and efficacy of these cells as a potential neuroprotective treatment for secondary progressive multiple sclerosis.

METHODS:
Patients with secondary progressive multiple sclerosis involving the visual pathways (expanded disability status score 5·5-6·5) were recruited from the East Anglia and north London regions of the UK. Participants received intravenous infusion of autologous bone-marrow-derived mesenchymal stem cells in this open-label study. Our primary objective was to assess feasibility and safety; we compared adverse events from up to 20 months before treatment until up to 10 months after the infusion. As a secondary objective, we chose efficacy outcomes to assess the anterior visual pathway as a model of wider disease. Masked endpoint analyses was used for electrophysiological and selected imaging outcomes. We used piecewise linear mixed models to assess the change in gradients over time at the point of intervention. This trial is registered with ClinicalTrials.gov, number NCT00395200.

FINDINGS:
We isolated, expanded, characterised, and administered mesenchymal stem cells in ten patients. The mean dose was 1·6×10(6) cells per kg bodyweight (range 1·1-2·0). One patient developed a transient rash shortly after treatment; two patients had self-limiting bacterial infections 3-4 weeks after treatment. We did not identify any serious adverse events. We noted improvement after treatment in visual acuity (difference in monthly rates of change -0·02 logMAR units, 95% CI -0·03 to -0·01; p=0·003) and visual evoked response latency (-1·33 ms, -2·44 to -0·21; p=0·020), with an increase in optic nerve area (difference in monthly rates of change 0·13 mm(2), 0·04 to 0·22; p=0·006). We did not identify any significant effects on colour vision, visual fields, macular volume, retinal nerve fibre layer thickness, or optic nerve magnetisation transfer ratio.

INTERPRETATION:
Autologous mesenchymal stem cells were safely given to patients with secondary progressive multiple sclerosis in our study. The evidence of structural, functional, and physiological improvement after treatment in some visual endpoints is suggestive of neuroprotection.

FUNDING:
Medical Research Council, Multiple Sclerosis Society of Great Britain and Northern Ireland, Evelyn Trust, NHS National Institute for Health Research, Cambridge and UCLH Biomedical Research Centres, Wellcome Trust, Raymond and Beverly Sackler Foundation, and Sir David and Isobel Walker Trust.

2012-02-02T18:34:55+00:00 February 2nd, 2012|Multiple Sclerosis, News, Stem Cell Research|