Development of innovative treatment targeted for CD40 ligand for patients with multiple sclerosis

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16109
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Chiba University
• Principal Investigator: Masuda Hiroki 千葉大学, 医学部附属病院, 特任助教 (10722936)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 血液脳関門 / 多発性硬化症 / 可溶型CD40リガンド / 実験的アレルギー性脳脊髄炎

Outline of Final Research Achievements

To elucidate the potential role of soluble CD40 ligand (sCD40L) in blood brain barrier (BBB) disruption in patients with multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) mice. Serum sCD40L levels, which was higher in patients with MS than in disease controls (DCs), was positively correlated with Qalb, a marker of BBB breakdown [median, 2480 versus 786 pg/mL; interquartile range (IQR), 2590 vs 1379; P = 0.046]. EAE scores of mice receiving high-dose sCD40L were worse than those receiving low-dose sCD40L and controls. Permeability coefficient was increased by sCD40L treatment in the human brain microvascular endothelial cell based BBB model (median, 2.43 vs 1.78 10-3cm/min; IQR, 0.85 vs 0.64; P = 0.032). As conclusion, sCD40L may facilitate inflammation in MS and EAE by BBB disruption.

Free Research Field

神経免疫疾患

Academic Significance and Societal Importance of the Research Achievements

多発性硬化症（MS）患者は再発寛解を繰り返しながら神経学的後遺症が蓄積していき、認知機能障害をきたしたり、車椅子や寝たきりになるなど日常生活動作の低下をきたすことが知られている。今回の研究によって、sCD40L がMS の急性期に上昇して血液脳関門破綻を促進し、重症化につながっているということが示唆された。そのため、今後、sCD40L をターゲットとしたMS 急性期の新規治療を確立することで、MS 患者の神経学的後遺症を軽症化することが可能になると予想される。すなわち、本研究の成果は世界で250 万人いるMS 患者の大きな福音になりうる。