Verification of the therapeutic effect of the neurotrophic factor pleotropin on ALS/FTLD pathology

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15622
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Shiga University of Medical Science (2022-2023); Nagoya University (2021)
• Principal Investigator: Fujioka Yusuke 滋賀医科大学, 神経難病研究センター, 助教 (70896381)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: プレオトロピン / FUS / グリア細胞 / ALS/FTLD

Outline of Final Research Achievements

To demonstrate the utility of a unique therapeutic strategy to preserve and harness the neuroprotective effects of glial cells in the early stages of ALS/FTLD disease, we tested recombinant pleiotropin supplementation (periodic intrathecal administration) as a means of providing sufficient amounts of pleiotropin to the peri-neuronal degenerating cells. Pathological studies confirmed that there were no significant adverse effects associated with intrathecal/intracerebroventricular administration of recombinant pleiotropin. Intrathecal administration of recombinant pleiotropin to SOD1 mutant mice was performed and changes in survival and motor function were confirmed. In addition, we pathologically confirmed the increased expression of pleiotropin and some neuroprotective effects in glia-specific FUS knockdown.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

筋萎縮性硬化症/前頭側頭葉変性症(ALS/FTLD)は未だ致死性の神経難病であり新規治療法の確立は急務である。我々が今回着目したプレオトロピンはFUS機能喪失時に生理的に機能する神経保護因子であるが、検討により治療効果、副作用の面で十分期待ができるものであった。本課題を通じプレオトロピンのALS/FTLDへの治療応用への道筋を示した社会的意義は大きい。