Stem cell therapy of multiple sclerosis is associated with immune modulation, as well as the possibility of inducing regeneration of damaged neural tissue.  In the quest to figure out novel agents that may be useful in combination with stem cell therapy, scientists assess various drugs.  One class of interesting drugs to evaluate are drugs that are already on the market for different diseases.  For example, erythropoietin was previously demonstrated to inhibit multiple sclerosis in animal models.  Erythropoietin is a hormone made by the kidneys that normally stimulates red blood cell production from the bone marrow hematpoietic stem cell.  Erythropoietin is administered as a drug in patients with anemia to increase red blood cells.  Interestingly, erythropoietin is also associated with suppression of inflammatory Th1 and Th17 responses, upregulation of antiinflammatory Th2 responses, and stimulation of endogenous stem cells, including stem cells in the brain. 

The video above describes the effects of lithium on the animal model of multiple sclerosis called experimental allergic encephalomyelitis (EAE).  It demonstrates that administration of lithium suppresses autoreactive T cells but not overall T cell responses.  Furthermore, the paper demonstrated that lithium administration not only suppressed disease onset, but also reversed established disease. 

It appears that lithium mediates its effects through the suppression of the GSK-3 enzyme, which is involved not only in inflammation but also self-renewal of stem cells. 

The above video is provided for educational purposes only and is not suggesting the use of lithium in treatment of multiple sclerosis patients, it is only providing some scientific information that may be useful in future clinical trials and scientific experiments.

We have previously discussed that one of the mechanisms by which mesenchymal stem cells may have therapeutic activity on multiple sclerosis is through stimulation of T regulatory cells.  In our publication we previously demonstrated that adipose derived cells, which are known to contain mesenchymal stem cells also contain high concentrations of T regulatory cells.

A recent publication (Royal et al. Peripheral blood regulatory T cell measurements correlate with serum vitamin D levels in patients with multiple sclerosis. J Neuroimmunol 2009 Jun 16) assessed circulating levels of 1, 25-dihydroxyvitamin D (1, 25-(OH)2 vitD) and 25-hydroxyvitamin D (25-OH vitD), which are metabolites of vitamin D.  Specifically, 25-OH VitD  (also called calcidiol) is made by chemical modification (hydroxylation) of VitD3 by the liver. Calcidiol made into the active form of vitamin D (calcitriol) by the kidney in a process mediated by the enzyme 25(OH)D-1 alpha hydroxylase. 

So there are two forms of vitamin D: a) Calcidiol and b) Calcitriol. 

The paper demonstrated a positive relationship between high levels of calcitriol and number of T regulatory cells were seen.

The possibility that Vitamin D is related to inhibiting multiple sclerosis comes from some other sources as well.  For example the paper (Correale et al. Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 2009 May;132(Pt 5):1146-60) makes the following interesting points:

1.  There are reports of diminished multiple sclerosis risk associated with sun exposure and use of Vitamin D supplements.

2.  Circulating levels of vitamin D have been associated with reduced risk.

3.  Out of 60 controls and 132 patients with multiple sclerosis the levels of Vitamin D, both calcitriol and calcidiol were lower as opposed to control.

4.  Patients during relapse had lower vitamin D.

5.  Calcitriol inhibited proliferation of T cells in vitro, stimulated IL-10, and reduced number of cells making IL-17.

6.  T cells can make calcidiol into calcitriol.

7.  Calcitriol increases indoleamine 2,3-dioxygenase activity.

8.  Calcitriol increases Treg cells in vitro.