Study using patient iPSC drug repositioning model for rare relentless prion gene mutated disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15231
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Jichi Medical University
• Principal Investigator: Matsuzono Kosuke 自治医科大学, 医学部, 講師 (80809070)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 神経難病 / プリオン / iPS細胞

Outline of Final Research Achievements

Prion disease is the fetal neurological relentless disease. Due to the rarity, it is hard to develop the treatment for this rare prion disease. For finding the effective treatment, we studied the using patient iPSC drug repositioning approach. We developed three each iPSC clone from the 58 age PRNP Y162X variant female and 63 age healthy control female. We differentiated these iPSCs to cortical neurons and found the effective drug for the PRNP Y162X variant case by using these iPS-neurons for disease modeling, Finally, we show that using PRNP Y162X patient iPSC drug repositioning model was available not only in basic but also in actual prion disease case, which can be the breakthrough approach for rare neurological relentless disease.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

プリオン遺伝子患者からiPS細胞を樹立して行った研究は世界でも稀少である。本研究ではプリオン病の中でも稀少なY162X変異例からiPS細胞の樹立に成功したが、その結果正常なプリオン蛋白が神経細胞にとって酸化ストレス耐性を獲得する上で重要な機能を果たしていることが明らかとなった。実際の患者に対して、研究の結果同定したエダラボンの投与を行ったところ、延命と症状改善効果が得られており、社会に与えるインパクトが大きい研究である。