High Dose Pharmaceutical Grade Biotin (MD1003) Accelerates Differentiation of Murine and Grafted Human Oligodendrocyte Progenitor Cells In Vivo.

Accumulating evidences suggest a strong correlation between metabolic changes and neurodegeneration in CNS demyelinating diseases such as multiple sclerosis (MS). Biotin, an essential cofactor for five carboxylases, is expressed by oligodendrocytes and involved in fatty acid synthesis and energy production. The metabolic effect of biotin or high-dose-biotin (MD1003) has been reported on rodent oligodendrocytes in vitro, and in neurodegenerative or demyelinating animal models. However, clinical studies, showed mild or no beneficial effect of MD1003 in amyotrophic lateral sclerosis (ALS) or MS. Here, we took advantage of a mouse model of myelin deficiency to study the effects of MD1003 on the behavior of murine and grafted human oligodendrocytes in vivo. We show that MD1003 increases the number and the differentiation potential of endogenous murine oligodendroglia over time. Moreover, the levels of MD1003 are increased in the plasma and brain of pups born to treated mothers, indicating that MD1003 can pass through the mother's milk. The histological analysis of the grafted animals shows that MD1003 increased proliferation and accelerates differentiation of human oligodendroglia, but without enhancing their myelination potential. These findings provide important insights into the role of MD1003 on murine and human oligodendrocyte maturation/myelination that may explain the mitigated outcome of ALS/MS clinical trials.

The effect of vitamin A supplementation on stimulated T-cell proliferation with myelin oligodendrocyte glycoprotein in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease whereby myelin sheath of the central nervous system is destroyed. Vitamin A is known to play a role in the immune system. It has been recognized that some metabolites of vitamin A can be used effectively to treat experimental autoimmune encephalomyelitis (EAE). AIMS: The effect of vitamin A as retinyl palmitate on T-cell proliferation in MS patients. SETTING AND DESIGN: This study is a double blind clinical trial of two test groups over a period of 6 months. MATERIALS AND METHODS: Thirty five multiple sclerosis (MS) patients were divided into two groups. One group received 25,000 IU/day vitamin A (as retinyl palmitate) and the other group were administered a placebo. The peripheral blood mononuclear cells (PBMCs) were separated and stimulated with myelin oligodendrocyte glycoprotein (MOG) and phytohemagglutinin (PHA) before and after the trial period. BrdU calorimetric assay was performed to measure cell proliferation. STATISTICAL ANALYSIS: Analysis of covariance (ANCOVA) and paired t-test were used to analyze the data. RESULTS: Observations showed statistical significant differences in the reduction of cell proliferation in the presence of MOG and fetal calf serum (FCS) in the culture medium, between patients receiving vitamin A and the placebo (P = 0.046). Although, this difference was not significant between the two vitamin A and placebo groups in MOG treatment with human serum, a decrease was observed in the group of patients taking vitamin A supplements (P = 0.019). Phytohemagglutinin did not cause any change in cell proliferation between the two groups. CONCLUSION: The results suggest supplementation with retinyl palmitate in patients with MS reduce MOG stimulatory effects on T-cells.