Mesenchymal Stem Cell Treatment of Secondary Progressive Multiple Sclerosis: Phase 2a proof-of-concept study


Multiple sclerosis is a disease that results when the immune system attacks the myelin insulation that wraps and covers particular nerves.  It is, therefore, part of a larger group of diseases called “autoimmune diseases.”  Because multiple sclerosis involves nerves, it affects the brain, spinal cord, and some peripheral nerve as well.

Typically, multiple sclerosis (MS) affects women more than men, which is common for most autoimmune diseases.  It is most commonly diagnosed between ages 20 and 40, but can it show up in anyone at practically any age.  The main cause of the pathology of multiple sclerosis is immune system-mediated damage to the protective covering that surrounds some, though not all nerves, the  myelin sheath.  Myelin sheaths help nerves transmit their nerve impulses faster, and without it, nerve signals slow down or stop altogether.

Damage to the myelin sheath results from specific immune cells that recognize the myelin sheath as a foreign invader.  The attacks against the myelin sheath cause inflammation at the nerves.  Inflammation results from immune cell activities whereby activated immune cells secrete chemicals called “cytokines” that sound the alarm in the immune system.  These cytokines recruit other immune cells to the site of injury or infection and the cells make antibodies against the foreign substance and other cells gobble up the foreign substance and destroy it.  You can see why the nerves take such a beating during multiple sclerosis.

Why does this happen in the first place?  There is no clear answer to this question.  Clearly some people are more prone than others to develop multiple sclerosis.  Infection of the nerves by particular viruses that cause the immune system to recognize it as foreign is another possibility, and other blame environmental factors.

Over half the patients with multiple sclerosis have progressive disease characterized by accumulating disability, and there are no treatments for them. Several experiments have established the ability of mesenchymal stem cells to suppress the damaging effects of autoimmune disorders, and in acute and chronic animal models of multiple sclerosis mesenchymal stem cells have many beneficial effects.  A recent paper has reported attempts to determine the safety and efficacy of mesenchymal stem cells as a potential treatment for secondary progressive multiple sclerosis.  The paper is Connick, P., et al., “Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study,” Lancet Neurology 11(2): 2012:159-6. Paper

For this research, Connick and his colleagues recruited people from East Anglia and north London that suffered from secondary progressive multiple sclerosis that affects the visual pathway.  Because the ability to see is relatively easy to determine with eye tests, this population was a prime set of candidates for this study.  Study subjects received intravenous infusions of their own bone-marrow-derived mesenchymal stem cells.  Safety and feasibility were two of the factors that were examined in this study.

Side effects were examined from 20 months before treatment until up to 10 months after the infusion. Also, the eyesight of the patients was ascertained by eye tests, but the nerves were directly tested for their ability to send nerve impulses.  Multiple sclerosis prevents nerves from being able to form and propagate proper nerve impulses, and if this treatment works, then it should improve the ability of the nerves to form nerve impulses.

In ten patients, no serious side effects were observed (rashes after the injection and so on).  However, an improvement in visual acuity was observed in almost all the patients.  The field of vision increased, as did the ability of the nerves to form nerve impulses.  Color vision and the structure of the retina were no affected, but the increase in vision was significant.

Thus, autologous mesenchymal stem cells were safely administered to patients with secondary progressive multiple sclerosis, and there is even some evidence of structural, functional, and physiological improvement after treatment.  These data suggest that mesenchymal stem cells possibly modulate the immune response in these patients and protect the nerves.  While these results are preliminary, they certainly warrant further investigation.

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