2023-06-28 14:16:15
The successes are not yet great, and the number of test subjects in the double-blind, randomized phase 2 study with the first-generation over-the-counter antihistamine (reported by amsel.de) is also small. However, the method and active substance used in the US study might represent an important step on the way to remyelination. At the same time, the researchers propose an MRI biomarker to measure remyelination.
Restoring destroyed myelin, not in the scarred lesions themselves, but in the rest of the tissue, is a goal of many MS researchers. This would make it possible to at least partially reverse disabilities. So far, most approved MS drugs aim to prevent further inflammation, slow down the progression of the disease or – in the best case – stop it completely. Research has achieved a great deal in this area over the past few decades. But: Myelin that has already been destroyed remains destroyed, the axons of the nerve cells are defenseless without myelin and this can lead to restrictions in everyday life.
Biomarkers for remyelination
Protecting myelin, even rebuilding it, is far more difficult than preventing inflammation. Researchers around the world are working hard to find ways of remyelination. The Stanford University team has now taken at least a small step in this direction with further evaluations of the ReBUILD study.
Not only triggering the remyelination itself is difficult. Measuring them from the outside and thus assessing the success or failure of potential active ingredients is what it is all regarding. While the impact on disability is small in the case of the ReBUILD study. The so-called visually evoked potentials (VEP), i.e. the nerve conduction speed following triggering with visual stimuli, were measured here. But for the first time, as the team from California reports, it has been possible to demonstrate remyelination using magnetic resonance imaging (MRI).
Measure myelin water fraction in the corpus collossum
There were two groups in the rendomised, double-blind, cross-over study: Group 1 received clemastine for 90 days, followed by a placebo for 60 days; in group 2 it was exactly the opposite. Before the start, following 90 and following 150 days, measurements were taken using VEP and MRI. In the crossover assessment, Clemastine was shown to be significantly better than placebo.
The subjects were comparatively young (approx. 40), had not been ill for very long (on average 5 years) and had relatively few impairments (EDSS approx. 2).
In the VEP, the study achieved the primary end goal with a latency reduction of approximately 2 milliseconds. This is already known from an earlier publication (amsel.de had reported).
Particularly noteworthy here is the technique used by the scientists to measure the myelin: First, they specified the corpus callosum (the connection between the two hemispheres of the brain) as the site to be examined, because it has a high proportion of myelin per se and thus Re – and demyelination produces clearer results than other areas in the CNS. Then they measured the proportion of myelin on the corpus callosum using an MRI method that, according to their own assessment, was not too complex (and already known). The water content is measured here, since a lot of myelin also stores a lot of water, but a little less. The myelin water fraction (MWF) is measured.
Remyelination by clemastine
The result of the MWF reached the endpoint: Before treatment, the mean MWF values of the groups in the corpus callosum were similar (0.087 vs. 0.088). At 90 days, the mean MWF in patients on clemastine in Group 1 increased to 0.092 and continued to increase (to 0.094) two months following stopping treatment, indicating myelin repair.
In group 2, which took placebo for the first three months, the mean MWF value dropped to 0.082. With treatment over 2 months (months 4 and 5) the value increased up to 0.086.
However, no significant difference in MWF was observed in areas with lesions. This indicated that significant myelin repair was occurring in the normal-appearing white matter outside of the lesions, the research team said.
Clemastine: better not to take it on your own
Clemastine is a first-generation antihistamine and is used to treat hay fever. It is freely available. However, taking clemastine on your own is not a good idea. The active ingredient has a sedative effect, which was the only side effect in the small group of subjects. In addition to fatigue, no MS patient would want this side effect. Above all, however, there are also contraindications such as bladder emptying disorders, prostate hyperplasia, stomach ulcers, glaucoma, porphyria, cardiac arrhythmia, pregnancy, to name just a few, which also stand in the way of long-term use.
Conclusion: Larger studies of clemastine are needed to assess its use in multiple sclerosis. For example, a British study in combination with metformin is currently underway, and another study in San Francisco is planned; in total, clinicaltrials.gov currently lists 6 studies on clemastine.
The measurement method using MWF in the corpus collosum still has to be documented with larger amounts of data. Although the subjects in ReBUILD had the relapsing course (and were also taking immunomodulators), clemastine or MS-specified antihistamine developments might also be an option for patients with progressive/insidious courses.
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