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Oral Laquinimod for MS may reduce brain damage caused by neurodegeneration

Teva Pharmaceutical Industries Ltd. and Active Biotech have announced the publication of a pre-planned analysis of the Phase III ALLEGRO study demonstrating that once-daily oral laquinimod provides a beneficial impact on brain tissue damage, one of the most destructive aspects of multiple sclerosis. These data, "Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage," published online in September by the Journal of Neurology, Neurosurgery & Psychiatry (JNNP), along with an accompanying editorial titled, "Oral laquinimod for multiple sclerosis: beyond the anti-inflammatory effect........." - Read More - http://www.ms-uk.org/laquinimod

Here is some information on the mechanism of action of laquinimod. As the information states, Laquinimod appears not to suppress the immune system, but rather to act as an immunoregulator. It suppresses the proliferation of the inflammatory cytokines tumor necrosis factor and interferon-gamma.

Tumor necrosis factor is a normal, necessary part of the immune system. However, excess levels of tumor necrosis factor can have many damaging effects. Since it is a necessary part of the immune system, it is important not to block or suppress it completely, but rather it should be properly regulated. For example, elevated levels of prolactin are very much involved in the MS disease process, but the answer is not to "block" prolactin, as it also has important roles in immune system function. It does however need to be properly regulated.

Profile of oral laquinimod and its potential
in the treatment of multiple sclerosis.

Mechanism of action
...Studies in both mice and humans have demonstrated
that laquinimod does not suppress the immune system;17
rather, it appears to act as an immunoregulator. Multiple
studies have suggested that laquinimod alters the balance
between inflammatory Th1-mediated cytokines in favor of a
more Th2-mediated anti-inflammatory cytokine profile.
Initial work with the compound in experimental autoimmune
neuritis first demonstrated this proposed shift. In an
EAN mouse model, Zou et al18 demonstrated suppression
of T cell proliferation with a significant decrease in cells
expressing interferon-gamma (IFN-γ) and tissue necrosis
factor-α (TNF-α) in sciatic nerves, with an increase in cells
expressing interleukin (IL)-4. They concluded that the drug
may shift the cytokine profile from inflammatory to antiinflammatory
and affect T cell differentiation.


Similar results have been found in EAE models. In
Lewis rats with EAE, there was a downregulation of cells
expressing TNF-α and IL-12, with upregulation of cells
expressing IL-4, transforming growth factor-beta (TGF-β),
and IL-10 mRNA.12 Both TNF-α and IL-12 are cytokines
involved in inflammation, with IL-12 playing a key role in
induction of the Th1 immune response and increased production
of other inflammatory cytokines, such as IFN-γ and
TNF-α.19 IL-4 is an important anti-inflammatory cytokine
that induces differentiation of naïve helper T cells to
Th2 cells and suppresses IFN-γ and TNF-α,20 while TGF-β
and IL-10 affect activation of lymphocytes and monocytes
and downregulate expression of Th1 cytokines, with spinal
cord sections also demonstrating decreased infiltrates of
CD4+ T cells and macrophages.