2019 Fiscal Year Final Research Report
Detecting early-stage biomarker of multiple sclerosis using Imaging Mass Spectrometry
| Project/Area Number |
17K09786
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Doshisha University |
|---|
Principal Investigator |
Ikegawa Masaya 同志社大学, 生命医科学部, 教授 (60381943)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
近藤 誉之 京都大学, 医学研究科, 准教授 (50322756)
角田 伸人 同志社大学, 生命医科学部, 助教 (50544615)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Keywords | 多発性硬化症 / イメージング質量分析 / プロテオミクス / 実験的自己免疫性脳脊髄炎 / バイオマーカー |
|---|
| Outline of Final Research Achievements |
Experimental autoimmune encephalomyelitis (EAE) is the most commonly used experimental model for the human inflammatory demyelinating disease, multiple sclerosis (MS). In this study, we applied matrix-assisted laser desorption/ionization (MALDI) mass imaging mass spectrometry (IMS) for EAE mice brain and spinal cord at proteome level. By single peak analysis, we have found a few protein markers that co-localized with immune cell infiltrations in cerebellum, hippocampus as well as spinal cords of the pre-symptomatic to symptomatic EAE animals, which disappeared at the chronic phase. To functionally test this hypothesis, we blocked the protein signals with a small molecule compound, a kind of immunosuppressant, before and after the onset of EAE symptoms to estimate its efficiency by a conventional clinical scoring method and histopathology. With this strategy, we have succeeded in obtaining a novel therapeutic target of multiple sclerosis as well as biomarkers through IMS.
|
| Free Research Field |
ゲノム医科学
|
| Academic Significance and Societal Importance of the Research Achievements |
イメージング質量分析法を用い、多発性硬化症モデルマウス脳・脊髄におけるin situ 組織プロテオーム解析の結果、病気の症状の現れる直前からすでに脳内には一群の免疫細胞の浸潤が認められ、これらの細胞と局在の一致するタンパク質・ペプチドを特定し、さらに免疫組織学的に検証に成功した。本研究は、これらの候補分子の中から最もよく脳病理を反映していると考えられるタンパク質のシグナルをブロックするような薬剤をEAEに予防投与と治療投与を行い、その両方で顕著な効果を確認した。今後はヒトへの応用可能性について検討する必要を認め、神経難病の新たな症状改善薬の開発の発端となることは社会的に意義深いと考えられる。
|
