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Vitamin D may increase the therapeutic benefits of glucocorticosteroids (GCs) for multiple
sclerosis (MS) through a protein complex called mTORc1, according to a study in a mouse
model and in cells from MS patients.
GCs are typically used in the treatment of acute MS relapses. However, more than 40
percent of these patients experience increased disability despite the treatment.
The team used a mouse model of MS with or without the glucocorticoid receptor and
mTORc1 — which responds to GC treatment — specifically in T-cells. In addition, the role
of the JNK signaling pathway — which inhibits glucocorticoid receptor-mediated gene
expression and is a major target of GC’s anti-inflammatory effect — was analyzed in
human T-cells using a JNK-inhibitor known as SP600125.
Results revealed that the serum levels of vitamin D were lower in GC-resistant MS patients
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than in GC-responsive and stable MS patients. This finding was associated with a lower
production of glucocorticoid receptor in T-cells.
Researchers also found that, in T-cells from MS patients during GC-resistant relapse, a
combination of vitamin D and GC boosts T-cell apoptosis by approximately 10% in
comparison to stand-alone GC therapy. The combination approach also eased the disease
course in mice more efficiently than treatment with either approach alone, a benefit
dependent on the presence of glucocorticoid receptors in T-cells.
Overall, the team concluded that vitamin D “increases therapeutic effects of GCs via a
mTORc1 dependent upregulation of the GR [glucocorticoid receptor]. These data suggest
that efficacy of GC in treatment of MS relapses could be improved by mTORc1 inhibition.”
Of note, nine of the study’s authors received research or travel grants, speaker honoraria,
or compensations from several companies, including Novartis, Biogen, Merck, Almirall,
and Sanofi Genzyme.
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