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Research: Alpha-4 Integrin Inhibitors (e.g., Tysabri) May Sponsor Remyelination

Posted on http://www.thisisms.com

Loosely defined, Alpha (4) beta (1) integrin is a protein on the surface of immune cells that allows them to pass into the central nervous system (CNS). In the auto-immune model of multiple sclerosis, these immune cells then mistakenly attack myelin, causing inflammation and the cascade that leads to scarring (or sclerosis) of the CNS.
A drug wich binds with the alpha (4) beta (1) integrin protein will prevent the immune cell from entering the CNS. The auto-immune theory would then predict that inflammation would be circumvented as the immune cells are not present in the CNS to attack myelin.

Tysabri, though currently unavailable whilst the PML issue is worked out, is the first alpha (4) beta (1) integrin binder available for multiple sclerosis patients. A new and very interesting study shows that prolonged exposure to an alpha-integrin inhibitor allows spontaneous remyelination to occur in the mouse model of MS versus vehicle alone (no active drug). In other words, preventing the immune system cells from reaching the CNS allows the body to repair damage better than when the immune cells are present.

Specifically, after 40 days of treatment with an alpha-integrin inhibitor (not necessarily Tysabri, though the study was partially funded by Tysabri´s part-owner Elan...), nearly 90% of the mouse lesions showed some form of remyelination. Further details include the repair occurring in just half of the total lesion areal, and half of the mice regaining motor function lost prior to treatment. The control mice did not show significant signs of repair or regaining of function. The study concludes: "Therefore, prolonged inhibition of CNS inflammation, in the absence of targeted myelin repair, facilitates mechanisms of spontaneous remyelination."

As with any study that is performed on mice, please remember that the mouse model of MS is oftentimes very different than the human version, and thus results on the animals do not necessarily predict results on humans. Likewise, prolonged inhibition of immune cell trafficking might also have unintended consequences, e.g., PML or another new study that shows chronic inhibition initially helps, then exacerbates colitis in mice.

In any case, this is an important study and shows that there is hope for repair of damage, particularly when the immune cells are mostly prevented from trafficking into the CNS.
Submitted  8/29/2005 12:51:16 PM