New Drug May Prevent Development and Reduce Progression of Multiple Sclerosis: Mouse Study

Summary: According to a new study, an experimental drug called laquinimod may help to prevent the development of and reduce the progression of multiple sclerosis.

Source: AAN.

The experimental drug laquinimod may prevent the development or reduce the progression of multiple sclerosis (MS) in mice, according to research published in the September 21, 2016, online issue of Neurology: Neuroimmunology & Neuroinflammation.

“These results are promising because they provide hope for people with progressive MS, an advanced version of the disease for which there is currently no treatment,” said study author Scott Zamvil, MD, PhD, of the University of California, San Francisco and a Fellow of the American Academy of Neurology.

In a proper immune response, T cells and B cells help the body develop immunity to prevent infection. But in MS, an immune and neurodegenerative disorder, those cells can help create antibodies that attack and destroy myelin, the protective, fatty sheath that insulates nerves in the brain and spinal cord.

For this research, the investigators studied mice that develop a spontaneous form of MS. Mice were either given daily oral laquinimod or a placebo (water). The number of T cells and B cells were then examined.

In one study of 50 mice, only 29 percent of the mice given oral laquinimod developed MS as opposed to 58 percent of the mice given the placebo, evidence the drug may prevent MS. Plus, there was a 96-percent reduction in harmful clusters of B cells called meningeal B cell aggregates. In people, such clusters are found only in those with progressive MS.

In a second study of 22 mice, researchers gave laquinimod after mice developed paralysis and observed a reduction in progression of the disease. When compared to the control, mice given the drug showed a 49-percent reduction in dendritic cells that help create special T cells called T follicular helper cells, a 46-percent reduction in those T cells and a 60-percent reduction in harmful antibodies.

Image shows a T cell.

In a proper immune response, T cells and B cells help the body develop immunity to prevent infection. But in MS, an immune and neurodegenerative disorder, those cells can help create antibodies that attack and destroy myelin, the protective, fatty sheath that insulates nerves in the brain and spinal cord. Neurosciencenews image is for illustrative purposes only. Credit: NIAID/NIH.

“This study has given us more insight into how laquinimod works,” Zamvil said. “But because this was an animal study, more research needs to be done before we know if it could have similar results in people.”

About this multiple sclerosis research article

Funding: The study was supported by the National Institutes of Health and the National Multiple Sclerosis Society. Teva Pharmaceuticals provided the drug.

Source: Renee Tessman – AAN
Image Source: This NeuroscienceNews.com image is in the public domain. Credit: NIAID/NIH.
Original Research: Full open access research for “Treatment of spontaneous EAE by laquinimod reduces Tfh, B cell aggregates, and disease progression” by Michel Varrin-Doyer, Kara L. Pekarek, Collin M. Spencer, Claude C.A. Bernard, Raymond A. Sobel, Bruce A.C. Cree, Ulf Schulze-Topphoff, and Scott S. Zamvil in Neurology: Neuroimmunology & Neuroinflammation. Published online September 21 2016 doi:10.1212/NXI.0000000000000272

Cite This NeuroscienceNews.com Article
AAN. “New Drug May Prevent Development and Reduce Progression of Multiple Sclerosis: Mouse Study.” NeuroscienceNews. NeuroscienceNews, 22 September 2016.
<http://neurosciencenews.com/neuropharmacology-multiple-sclerosis-5104/>.
AAN. (2016, September 22). New Drug May Prevent Development and Reduce Progression of Multiple Sclerosis: Mouse Study. NeuroscienceNews. Retrieved September 22, 2016 from http://neurosciencenews.com/neuropharmacology-multiple-sclerosis-5104/
AAN. “New Drug May Prevent Development and Reduce Progression of Multiple Sclerosis: Mouse Study.” http://neurosciencenews.com/neuropharmacology-multiple-sclerosis-5104/ (accessed September 22, 2016).

Abstract

Treatment of spontaneous EAE by laquinimod reduces Tfh, B cell aggregates, and disease progression

Objective: To evaluate the influence of oral laquinimod, a candidate multiple sclerosis (MS) treatment, on induction of T follicular helper cells, development of meningeal B cell aggregates, and clinical disease in a spontaneous B cell–dependent MS model.

Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by immunization with recombinant myelin oligodendrocyte glycoprotein (rMOG) protein. Spontaneous EAE was evaluated in C57BL/6 MOG p35-55–specific T cell receptor transgenic (2D2) × MOG-specific immunoglobulin (Ig)H-chain knock-in (IgHMOG-ki [Th]) mice. Laquinimod was administered orally. T cell and B cell populations were examined by flow cytometry and immunohistochemistry.

Results: Oral laquinimod treatment (1) reduced CD11c+CD4+ dendritic cells, (2) inhibited expansion of PD-1+CXCR5+BCL6+ T follicular helper and interleukin (IL)-21–producing activated CD4+CD44+ T cells, (3) suppressed B cell CD40 expression, (4) diminished formation of Fas+GL7+ germinal center B cells, and (5) inhibited development of MOG-specific IgG. Laquinimod treatment not only prevented rMOG-induced EAE, but also inhibited development of spontaneous EAE and the formation of meningeal B cell aggregates. Disability progression was prevented when laquinimod treatment was initiated after mice developed paralysis. Treatment of spontaneous EAE with laquinimod was also associated with increases in CD4+CD25hiFoxp3+ and CD4+CD25+IL-10+ regulatory T cells.

Conclusions: Our observations that laquinimod modulates myelin antigen–specific B cell immune responses and suppresses both development of meningeal B cell aggregates and disability progression in spontaneous EAE should provide insight regarding the potential application of laquinimod to MS treatment. Results of this investigation demonstrate how the 2D2 × Th spontaneous EAE model can be used successfully for preclinical evaluation of a candidate MS treatment.

“Treatment of spontaneous EAE by laquinimod reduces Tfh, B cell aggregates, and disease progression” by Michel Varrin-Doyer, Kara L. Pekarek, Collin M. Spencer, Claude C.A. Bernard, Raymond A. Sobel, Bruce A.C. Cree, Ulf Schulze-Topphoff, and Scott S. Zamvil in Neurology: Neuroimmunology & Neuroinflammation. Published online September 21 2016 doi:10.1212/NXI.0000000000000272

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