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MRI Technique Shows Success of MS Drug Copaxone

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Using magnetization transfer ratio (MTR) researchers found a reduction in contrast enhancing lesions, possibly inducing remyelination.

Using an unconventional MRI technique, researchers found the multiple sclerosis medication glatiramer acetate (Copaxone) reduced contrast enhancing lesions (CEL), possibly inducing remyelination, or restoration of damaged nerve sheaths. In a study published in the January Frontiers in Bioscience, researchers used magnetization transfer ratio (MTR) to observe the change in CELs over time, finding an increase of MTR in all three lesion subgroups.

The study examined 40 patients with relapse remitting multiple sclerorsis (RRMS), who had a total of 115 contrast enhancing lesions (CEL) at baseline. Each of the subjects (all Copaxone-naïve) received Copaxone for 12 months, and underwent clinical examination in addition to conventional MRI and MTR protocols at baseline and 12 months. After the one-year MRI, researchers found only 21 CELs. The study, conducted at the Buffalo Neuroimaging Analysis Center (BNAC) at the University at Buffalo, State University of New York was an open-label, single-blinded post-marketing observational study.

“Although it was a very small number of patients, and only 115 lesions, I think this study provides good confidence that glatiramer acetate may be promoting remyelination in those active lesions,” said study lead Robert Zivadinov, MD, PhD, Director of the BNAC, and Professor of Neurology at the University at Buffalo.

Magnetization transfer ratio is an emerging technique to assess remyelination in the brains of MS patients, said Zivadinov. It’s used to look at brain structure abnormalities. “By using the nonconventional MTR techniques, we showed you can provide improvement in these lesions, and we’re pretty confident that this improvement is linked to remyelination,” said Zivadinov.

While the findings are promising, not everyone agrees with Zivadinov’s conclusion that the medication induced remyelination. “It’s seemingly a great medication and a valuable paper in that they reduced inflammation. But to go as far as to say the tissue is repaired, I don’t think you can do that,” said Christopher Hancock, MD, director of neuroradiology at Desert Medical Imaging in Palm Springs, Calif.

“They’re trying to say that if the signal has changed in that area because of Copaxone, then there’s been an improvement. If your metric is reduction in inflammation, yes. But they’re saying tissue repair, so I’m not convinced. I think they’re extrapolating too much. I don’t think their conclusions are based on rigorous scientific fact. How do you know [the tissue is repaired]? Did you do a biopsy?”

No biopsies were done on these subjects. Zivadinov said, however, that animal studies documented in the literature have used MTR to show that remyelination was induced (not with glatiramer acetate, but with animal models). He said that the increase in MTR in those studies was linked to the remyelination found in the animal pathology.

In this study, Zivadinov did not think the MTR increase was due to edema resolution. “We scanned (with MRI) after one year, so I would argue that the changes of the MTR are probably not likely due to the edema resolution but more likely to the remyelination, because you’d largely expect that the edema would be resolved over one year.” He added that edema usually resolves after 10-20 days of treatment, so if there is a signal improvement after one year, it’s probably more likely linked to remyelination. “The longitudinal studies have suggested that remyelination might be very frequent in some kinds of multiple sclerosis.”

Though MTR is an unusual technology to track MS lesions, is it gaining a foothold in clinical MS treatment? Not likely. “I think that MTR is definitely a more related research tool for certain drugs,” said Zivadinov. “I think that it will be difficult to apply this method in clinical routine because it requires extra processing and interpretation. We’re not there yet.”

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