Research press release


Nature Communications

Health sciences: Antidepressant shows potential for multiple sclerosis treatment in mouse model



今回、Voon Wee Yongたちの研究グループは、1040点の医薬品のライブラリのスクリーニングを行い、血液脳関門を通過できる経口ジェネリック医薬品(249点)を選択した。これら249種類の化合物については、培養細胞において神経毒性を防止し、Tリンパ球の増殖を抑制し、抗酸化活性を有する化合物を発見するためのスクリーニングがさらに実施されて、経口抗うつ薬のクロミプラミンが特定された。クロミプラミンは、マウスの実験において、多発性硬化症のモデルである自己免疫性脳脊髄炎の症状を軽減した。


A systematic screening of generic, orally taken medications to identify drugs with the potential to be repurposed for the treatment of progressive multiple sclerosis is reported in Nature Communications this week. Using this approach, the authors identified clomipramine, an orally-taken antidepressant, which reduces the symptoms of autoimmune encephalomyelitis, a mouse model of multiple sclerosis.

Multiple sclerosis is a multifactorial inflammatory disease affecting the central nervous system, which causes damage to the myelin sheath (a layer of fatty insulation that protects nerve cells), and neurons, and is associated with severe neurological symptoms. Up to 15% of patients with multiple sclerosis have a progressive form of the disease for which treatment options are limited. One reason is that the disease is multifactorial, and includes neurodegeneration, abnormal lymphocyte activity and oxidative stress, and these factors are not simultaneously targeted in current treatments.

Voon Wee Yong and colleagues screened a library of 1,040 medications and selected 249 that are taken orally, generic and can cross the blood-brain barrier. The 249 compounds were further screened to identify those that can, in cultured cells, prevent neurotoxicity, reduce T lymphocyte proliferation and have antioxidant activity. They identified clomipramine, which is an orally taken antidepressant, and show that in mice, it reduces the symptoms of autoimmune encephalomyelitis - a model for multiple sclerosis.

The authors note that there is no model of autoimmune encephalomyelitis that covers all aspects of progressive multiple sclerosis but clomipramine could be a candidate drug for further development.

doi: 10.1038/s41467-017-02119-6

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