Feb 11, 2002
Minocycline's ability to inhibit microglial migration and to suppress T-cell recruitment into the central nervous system appears to reduce neurologic deficits in a rat model of chronic relapsing-remitting multiple sclerosis (MS).
Dr. Ian D. Duncan, of the University of Wisconsin in Madison, and colleagues immunized rats with myelin oligodendrocyte glycoprotein (MOG) to induce experimental allergic encephalomyelitis (EAE). Clinical state between days 12 and 42 post-immunization was scored on a scale of 0 to 5, where 0.5 represented partial loss of tail tone, 3 represented hindlimb paralysis, and 5 represented death.
The mean cumulative score in EAE animals treated with placebo was 54.11, Dr. Duncan's group reports in the Annals of Neurology for February. For rats treated with minocycline from the 10th day after immunization, the severity of the initial phase of disease and the duration of subsequent relapses were suppressed. The cumulative score decreased to 7.43 (p < 0.001).
When the same dose was given from the day of clinical disease onset, mean cumulative score added up to 26.25, suggesting, the investigators write, that the drug can suppress established clinical disease.
The number of T cells in the spinal cords of minocycline-treated EAE rats was significantly reduced compared with sham-treated rats. Matrix metalloproteinase was absent in treated rats, while it was upregulated in areas of inflammation in the sham-treated rats.
The increase in matrix metalloproteinase expression was accompanied by the presence of rounded, activated microglia. Minocycline treatment resulted in most microglia exhibiting a resting state with long branched processes.
The researchers found that minocycline altered the MOG-specific autoimmune response, such that the counter-inflammatory cytokine IL-10 was increased in draining lymph nodes.
Minocycline "has the potential to be more effective than beta-interferon or glatiramer acetate," Dr. Duncan told Reuters Health. It could also represent a beneficial adjunct therapy, he added.
He and his associates speculate that minocycline "could be given to patients with relapsing-remitting disease early in its course, and prescribed for 1 to 3 months. We hope at that point it would block ongoing disease and that it would not have to be given as continuous therapy," he said.
Even if the course of the disease required ongoing therapy, he pointed out, it is very safe, having been used in the treatment of rheumatoid arthritis for months or years with minimal side effects.
Dr. Duncan described a clinical trial that has been initiated at the University of Calgary, which should provide initial results within 6 to 9 months. It is planned to run for 2 to 3 years.
The one caveat he offers is for physicians to avoid "jumping the gun" and prescribing minocycline for MS patients before results of the clinical trial are reported. Otherwise, "the results of the trial may become clouded if we begin getting anecdotal reports," he said, adding, "6 or 9 months is not that long to wait."
Ann Neurol 2002;51:215-223.
© 2002 Reuters Ltd