Making Gains in MS Drug Research

Multiple sclerosis drug laquinimod offers hope but needs study

(RxWiki News) A new medication for multiple sclerosis just got one step closer to being available for use. Researchers have published data that they believe shows exactly how the drug works in the brain.

Laquinimod is a drug that has been successfully studied in phase II/III trials for the treatment of relapsing-remitting multiple sclerosis (RRMS), but the exact mechanism of how the drug works in the body was not fully known.

Jan Thöne, MD, of the Department of Neurology at St. Josef-Hospital Bochum and Ruhr-University Bochum, Germany, and his colleagues found that laquinimod caused immune cells in the brain to produce a molecule called brain-derived neurotrophic factor (BDNF), which aided in the protection of neurons.

They also found that the drug had a modulatory effect on monocytes, a specific type of immune cell.

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Dr. Thöne and colleagues used a two-pronged approach to figure out laquinimod's action. First, they analyzed blood samples from 203 MS patients treated with laquinimod and measured the levels of BDNF. They found that 76% of the laquinimod-treated patients had an increase in the neurotrophic factor, with some patients experiencing an increase of 11-times greater than normal.

They then double checked the effects in mice. The researchers used mice that had experimental autoimmune encephalitis (EAE, a study model for MS) and divided them into two groups, mice with an immune cell deficiency in BDNF (LLF mice), and mice who did not (WT mice). 

The WT mice that were treated with laquinimod showed a significant improvement in the symptoms of EAE, while the LLF mice, who couldn't produce BDNF, had a very significantly reduced response to the drug. 

Pathologic examination of the mice showed that those treated with laquinimod showed a reduction in brain inflammation as well as a reduction in demyelination, the hallmark of MS. To show that the drug works by stimulating immune cells in the body (monocytes, in this case) the researchers injected laquinimod-stimulated monocytes directly into mice when they still had early-stage EAE. These mice, when compared to controls, showed less severe disease. When the same cells were injected into mice that could not produce BDNF, they had no impact.

Dr. Thöne explains the findings as such, "Consistent with immunomodulatory properties, laquinimod skewed monocytes towards a regulatory phenotype and also acted via modulation of BDNF, which may contribute to neuroprotection in MS patients".

Teva sponsored the German observational study, published online December 8 in the American Journal of Pathology.

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Review Date: 
December 10, 2011