How and why does nimodipine work?
Whether relapsing-remitting multiple sclerosis progresses to secondary progressive MS, which is characterized by a slow increase in neurological dysfunction, or if primary progressive MS is present, therapeutic options have been limited to date.
For this phase of MS, we are investigating the efficacy of the drug nimodipine.
Effect in animal model
So far, the drug has shown strong effectiveness in animal models: mice treated with nimodipine show a clinical improvement in their symptoms, and regeneration in the central nervous system is detectable. The next project goal is now to find out exactly how we can explain the effect of the drug. The hope is that if we can find out why nimodipine works, it could lead to the development of better drugs for progressive MS.
Past, present and future projects with nimodipine
(A) Microglial cells treated with nimodipine show mitochondrial changes. Electron micrographs show mitochondrial pathology in microglial cell line N9 as early as three hours after treatment with nimodipine. The scale bar indicates 5 µM. (B) In contrast to untreated cells, treatment with nimodipine results in increased numbers of oligodendrocytes in an in vitro culture system of myelination. The marker SMI31 labels axons in both images (red), whereas an antibody against myelin oligodendrocyte glycoprotein (MOG) was used to label myelin (green). (C) Potential effects of nimodipine on oligodendrocytes: nimodipine has a potential remyelinating effect on oligodendrocytes, although this effect probably does not occur via the canonical interaction partners of nimodipine, the voltage-gated calcium channels. Our data indicate, in addition to an increased expression of myelin proteins, a change in miRNA expression, a modulation of mitochondrial activity, and a reduction of cell stress upon treatment with nimodipine. In the future we want to investigate the influence of nimodipine on human neurons and glial cells and initiate clinical studies on the effect of nimodipine in progressive multiple sclerosis.
