Development of bifunctional catalytic antibody aiming at innovative therapeutic drug for Alzheimer's disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06486
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
• Research Institution: Suzuka University of Medical Science
• Principal Investigator: Taguchi Hiroaki 鈴鹿医療科学大学, 薬学部, 教授 (20549068)
• Co-Investigator(Kenkyū-buntansha): 一二三 恵美 大分大学, 全学研究推進機構, 教授 (90254606)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 抗体酵素 / アルツハイマー病 / アミロイド

Outline of Final Research Achievements

As the elderly population increases, the number of people with Alzheimer's disease is steadily increasing, making the development of treatment and preventive agents an urgent priority. The principal investigator aimed to develop a preventive and therapeutic agent for Alzheimer's disease, a condition for which there is currently no effective treatment and sought to produce catalytic antibodies targeting the causative molecules. An antibody light chain and a mutant form, in which the proline at position 95 of the antibody light chain was deleted, were engineered from an FDA-approved Alzheimer's drug. The hydrolytic activity of these antibody light chains was measured using a synthetic substrate, revealing hydrolytic activity in the mutant. Based on these findings, it was concluded that a catalytic antibody was successfully generated from an antibody drug.

Free Research Field

医薬品化学

Academic Significance and Societal Importance of the Research Achievements

効果的な治療薬がないアルツハイマー病の予防・治療薬の創製を目指し、アミロイドβに対する抗体医薬品より軽鎖抗体を作製し、軽鎖抗体より95位のProを除去することにより酵素活性の付与に成功した。抗体医薬品のアミロイド除去機構には、免疫細胞の関与が必要であるが、抗体酵素は単体でアミロイドの除去が可能である。また、抗体酵素１分子はその触媒作用により、生体内の半減期で多くのアミロイドを除去することができる。その結果、既存の抗体医薬に比べ、投与量を大幅に減少させることができる。このことから、抗体医薬品がかかえる副作用や高額な医療費などの問題を解決することが可能であり、社会的意義もあると考えている。