2021 Fiscal Year Final Research Report
A novel cell transplantation therapy for ALS using scFv-secreting OPCs
| Project/Area Number |
19H03573
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 52020:Neurology-related
|
|---|
| Research Institution | Shiga University of Medical Science |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
朝長 啓造 京都大学, ウイルス・再生医科学研究所, 教授 (10301920)
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | 筋萎縮性側索硬化症 / 抗体 / SOD1 / 移植 / ウイルスベクター / オリゴデンドロサイト前駆細胞 |
|---|
| Outline of Final Research Achievements |
Genetic mutations in SOD1 are the most prevalent familial ALS cause in Japan. We designed novel regenerative immunotherapy in which scFv from D3-1 hybridoma mRNA was subcloned into a Bornavirus disease vector (BoDV) to be introduced into oligodendrocytes precursor cells (OPCs-D3-1). We generated a monoclonal antibody against misfolded SOD1, named D3-1. First, we confirmed that intrathecal infusion of full-length D3-1 antibody into H46R SOD1 transgenic rats extended the longevity. Then we injected OPC-D3-1, OPC alone, and saline as procedural control into the cisterna magna of H46R SOD1 rats. Intracysternal transplantation of OPC-D3-1 markedly slowed progression and prevented the worsening of limb functions. Moreover, we observe marked amelioration of motor neuron loss and gliosis and reduction of neuromuscular junctions. Mutant SOD1 proteins were also reduced in the spinal cords. Transcriptome analyses demonstrated the downregulation of proinflammatory molecules.
|
| Free Research Field |
脳神経内科
|
| Academic Significance and Societal Importance of the Research Achievements |
遺伝子疾患に対する核酸治療の開発が進み、難病の治療展望に明るい光が見えてきました。我々の研究成果は変異遺伝子が作り出す蛋白質を治療標的と捉え、これまでの抗体治療の限界を細胞移植という全く異なる次元の治療法と融合させることによって、難病ALSに新しい治療の選択肢を提示しました。特に腫瘍原性や炎症を起こしにくいオリゴデンドロサイトを用いた抗体再生治療は世界初の成果です。
|
