Experimental Medications: Other Therapeutic Strategies
Vitamin D is a type of hormone and a powerful mediator of immune function. The data documenting an association between low Vitamin D and high MS risk, relapses, disability, and CNS inflammation now appear to be strong, consistent, and reproducible, including new data presented in 2013.70 Data from a number of areas of investigation suggest that Vitamin D may be one underlying common factor that begins to make sense of the large amount of data on the geographic distribution of susceptibility to MS.
Genetically, a link appears to exist between changes in the genes involved in the synthesis of the Vitamin D hormone and the Vitamin D hormone receptor, and the risk of developing MS. The strongest genetic risk factor for MS is a specific gene (HLA DRB1*1501), whose activity appears to be influenced by Vitamin D.
In animal models of MS, Vitamin D was found to directly terminate the production of disease-causing proteins, which may shed light on the mechanism of Vitamin D in MS. When Vitamin D is given to mice with EAE (an animal model of MS), it blocks the gene that encodes IL-17, stopping its production. IL-17 appears to be a major inflammatory component in MS. This study also demonstrates that Vitamin D increases suppressive T cells that combat inflammation.
An important longitudinal cohort study presented in 2012 by Mowry and colleagues71 found that in people with MS, each 10 ng/ml higher Vitamin D level was associated with a 15-percent lower risk of a new T2 lesion, and a 32-percent lower risk of a gadolinium-enhancing lesion. Higher Vitamin D levels were associated with lower, but not statistically significant, relapse rates. While this was not a randomized treatment trial, it suggests that higher levels of Vitamin D may exert a protective role against MS disease activity.
Similar data were presented in 2013, as researchers looked at how Vitamin D may play a role in MS development and disease activity on a molecular level. The BENEFIT trial, as discussed above, studied the effects of interferon beta-1b (Betaseron) in patients with CIS. Blood samples were taken at various intervals, along with MRIs.
This study found that individuals with higher Vitamin D levels had lower numbers of gadolinium-enhancing lesions. These individuals generally experienced less disease activity, and genes associated with these higher Vitamin D levels appear to be involved. Studies indicate that roughly 350 genes are “significantly associated” with MS activity, and of these 350 genes, 155 are associated with Vitamin D regulation. The authors of this study explain that Vitamin D may directly and indirectly regulate gene expression in a manner that reduces MS activity.
A number of new clinical trials, mostly using Vitamin D as an add-on to existing therapies in Phase IV studies, are ongoing to assess if supplemental Vitamin D can exert such disease-modifying effects. To follow are examples of these types of investigations.
Mowry and colleagues at Johns Hopkins have initiated a multi-center clinical trial in which patients with relapsing-remitting MS will receive high-dose (5,000 IU/day) or low-dose (600 IU/day) oral Vitamin D, in addition to Copaxone.72 Patients will be evaluated for two years, and the effect of high-dose Vitamin D supplementation on the rate of MS attacks as well as on the number of new lesions and changes in brain volume on MRI will be determined. This trial is presently enrolling, with a goal of 172 participants, and is expected to run through December 2016.
A Phase II study that has completed recruiting73 participants is investigating whether Vigantol® oil, a form of Vitamin D hormone supplement (cholecalciferol), provides any added benefit when given in conjunction with Rebif. The study will have 348 participants; it began in February 2011 and is scheduled for completion in May 2015. Primary outcome measures are the mean change from baseline in the total volume of T2 lesions at week 48 and the proportion of relapse-free subjects at week 96. Secondary outcome measures include sustained disability progression, MRI measures of disease progression, the proportion of subjects free from disease activity at 96 weeks, and changes in cognitive function.
The French CHOLINE Phase II study74 of 250 individuals with RRMS who are receiving ongoing treatment with Rebif began in January 2010 and is scheduled for completion in June 2015. The aim of this study is to evaluate the efficacy and safety of supplementary treatment with Vitamin D3 in people with RRMS treated with Rebif.
The study participants will be divided into two groups, one receiving Vitamin D3 100,000 IU twice monthly along with Rebif treatment, and the other group will be on placebo along with Rebif treatment. Its primary outcome measure is a reduction in relapse rate. Secondary outcome measures include: the time to a first documented relapse; the mean number of relapses per subject per year; the number of relapse-free patients after two years of treatment; MRI measures of progression and lesion load; and change in quality of life.
Please note that while no major safety issues have been reported with these larger daily doses of Vitamin D3 (such as 5,000 to 10,000 IU/day), as with all medications and supplements, individuals should always consult their physician before making any changes to their treatment plan.