The inflammatory disease, Multiple Sclerosis (MS), occurs when the body's own immune system attacks the myelin protective sheath covering nerve cells in the brain and spinal cord. Nerve cells are crucial for communication between the nervous system and therefore the irreversible damage results in a range of symptoms depending on the amount of nerves affected. Physical and mental symptoms are both shown, including the loss of ability to walk and slurred speech, but may disappear between attacks on the nerve cells.

There is still currently no cure for this debilitating disease and although there are treatments available which try to prevent future attacks or to improve nerve cell function, they are limited and often poorly tolerated. At present, available treatment involves immunosuppression in order to prevent de-myelination, but is associated with harmful side effects. There are no options available to promote re-myelination which would be a significant advancement in MS therapeutics.

Current research carried out by Kraig et al. at the University of Chicago concentrates on using exosomes, 30-100nm vesicles containing mRNA, microRNA and proteins, for therapeutic purposes [1]. To date, Scientists have been interested in exosomal diagnostic biomarkers for MS; however Kraig's team believes that they are also useful for treatment purposes.

Experiments carried out on rats showed that serum exosomes produced upon environmental enrichment, increased myelin sheath content (see Figure 1) and reduced oxidative stress in hippocampal slice cultures. An important finding was that aged rats were also able to increase the amount of myelination-promoting exosomes when exposed to environmental enrichment. Their work shows that increased myelination can occur in healthy rats using natural miRNA-containing exosomes, as well as re-myelination in a de-myelinated model in-vitro.

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Figure 1: Electron Micrographs showing myelin sheath thickness in slice cultures. Left: untreated control Right: Following treatment with exosomes. Photo credit: Kraig et al. (2014).

Microarrays were used in order to deduce the component inside these exosomes which was promoting re-myelination. High levels of miR-219 were found which are a necessary component for myelin formation and maintenance and increase oligodendrocyte precursor differentiation. When the exosomes reach their destination, the miRNA is able to regulate protein production via mRNA.

The authors concluded that this shows that is may be feasible to use donor cells to produce exosomes containing miR-219 to increase myelin production within the brain. The incorporation of specific anti-inflammatory miRNAs into these exosomes could also be used in conjunction to reduce any inflammation present. These are very promising results and represent the possibility of a novel therapeutic option for those suffering with MS, with scientists hoping to begin clinical trials within the next 5 years.

Citations:

[1] Kraig, R. P. et al. What are exosomes and how can they be used in multiple sclerosis therapy? (2014). Expert Rev. Neurother. 14: 353- 355.