Today's post from journals.lww.com (see link below) talks about spontaneous re-myelination in certain patients with nerve problems. Maybe first, we need to remind ourselves what myelin and myelination actually is. Myelin is the protective sheath around the nerve (axon) and in very many cases of nerve damage, it is the destruction or deterioration of this myelin sheath that causes the neurological problem. You can equate it to a live wire without its insulation. However, by using specialist PET scans, researchers have found that certain people spontaneously regenerate their own myelin and the implications of this may very well provide new forms of treatment for the future. They are looking for the agents involved in maintaining and regrowing myelin sheaths after they've been injured and if these are discovered, the potential for the future is clear.
BY DAN HURLEY Thursday, April 23, 2015
WASHINGTON—The first clinical trial of a positron emission tomography (PET) tracer previously shown to bind tightly to myelin in animal models of multiple sclerosis (MS) has identified previously unknown variations in patients’ capacity for remyelination, and has linked those differences to clinical outcomes, according to a paper presented here on Wednesday at the AAN Annual Meeting.
The study used PET with carbon-11 Pittsburgh compound B (11C-PiB), a radioactive compound originally developed as a marker of amyloid plaque but shown in a 2011 paper in the Annals of Neurology to work even better as an imaging marker of myelin loss and repair in animals.
The new study involved 20 patients with active MS who underwent both PET scans and a conventional magnetic resonance imaging (MRI) scan at baseline and at either two or four months later. Indices of myelin content change were statistically correlated with the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Scale (MSSS).
The study found no link between changes in demyelination and clinical scores, but identified a strong correlation between remyelination and both EDSS (r = -0.8, p=0.0001) and MSSS (r = -0.57, p = 0.009).
“Our results suggest that there might be an individual remyelination capacity for each individual, which allows them to respond more or less efficiently to a demyelinating insult,” the first author of the paper, Benedetta Bodini, MD, PhD, a neurologist and postdoctoral research fellow in the Brain and Spine Institute at the Hôpital Universitaire Pitié Salpêtrière in Paris, told the Neurology Today Conference Reporter ahead of the presentation.
“Even more interesting, when we correlated this remyelination potential with the clinical scores, we obtained very strong correlations, as if the clinical prognosis is very much influenced by the level of remyelination. If I’m a good remyelinator, I’m going to do better than someone who is not.”
If the findings stand up in larger trials, she said, “This tells us that we really need to shift our therapeutic strategies toward finding remyelinating medications.”
John R. Corboy, MD, FAAN, a professor of neurology at the University of Colorado School of Medicine and co-director of the Rocky Mountain MS Center at Anschutz Medical Campus, welcomed the results, but sounded a note of caution.
“This kind of marker is potentially quite useful,” said Dr. Corboy, who also serves on the Neurology Today editorial advisory board. “MRI scans frequently just tell us there’s been damage of some kind, whereas PET can be tied to very specific molecules on specific cells. If validated in further studies, having a radiological marker of improvement would be incredibly important, especially if it shows areas where you remyelinated brain.”
A study published earlier this year in Brain, he noted, used another PET tracer, PK-11195, to distinguish between activated and non-activated microglia in normal-appearing white matter of patients with clinically isolated syndrome.
“They showed that even in normal-appearing white matter, there was significant activation of microglia,” Dr. Corboy said. “The more activation seen, the higher the patient’s risk for developing MS over two years. So it was prognostic.”
Researchers are aggressively investigating PET markers not only for prognosis, but also to explore pathophysiology and as a means to show whether investigational therapies are working, Dr. Corboy said. “It’s extremely challenging, especially for patients with progressive MS, that we haven’t had a good way to measure improvement.”
A number of potential pro-myelinating agents are already being studied, Dr. Bodini pointed out, including anti-LINGO-1, olesoxime, clemastine, and retinoic acid receptor modulators.
However, Dr. Corboy said, “The phase 2 anti-LINGO-1 study was a little disappointing. It showed only some modest effects on speed of conduction, and did not meet its major outcome measure. Perhaps a marker like 11C-PiB would be useful by showing that perhaps clinical measures weren’t accurate enough.”
The 11C-PiB marker for myelin was developed by the senior author of the paper presented at the AAN meeting, Bruno Stankoff, MD, PhD, a professor of neurology at the Université Pierre et Marie Curie in Paris. Already, Dr. Bodini said, their team is developing another tracer that binds just as tightly to myelin but uses fluorinated compounds rather a carbon-labeled one. “Fluorinated compounds are much more accessible and allow the technique to be used much more widely in different centers,” she said.
For more articles on spontaneous remyelination, browse our archives here.
http://journals.lww.com/neurotodayonline/blog/NeurologyTodayConferenceReportersAANAnnualMeeting/pages/post.aspx?PostID=6
Tidak ada komentar:
Posting Komentar