| Project/Area Number |
18K06597
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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| Research Institution | International University of Health and Welfare (2020)
Kyushu University (2018-2019) |
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Principal Investigator |
Abe Yoshito 国際医療福祉大学, 福岡薬学部, 教授 (60315091)
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| Co-Investigator(Kenkyū-buntansha) |
山下 智大 九州大学, 薬学研究院, 助教 (30645635)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | P2X4 / 抗体 / 神経障害性疼痛 / タンパク質化学 / P2X4受容体 / モノクローナル抗体 / 蛋白質科学 / 痛み創薬 |
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| Outline of Final Research Achievements |
Molecules that have an inhibitory effect on P2X4 are considered to be "pain suppressor molecules" that can help patients suffering from neuropathic pain, which currently affects more than 20 million people worldwide. In addition, attempts are being made to expand the target by derivatization, in which drugs, enzymes, or proteins are added to the antibody. We have prepared a monoclonal antibody with a high affinity of 10 nM that recognizes P2X4 on the surface of rat microglial cells. This antibody specifically can recognize the structure near the ATP-binding site involved in the function of P2X4. For the purpose of pain suppression, we improved the preparation method of this high affinity antibody and developed a derivatized antibody by adding metal chelates or ATP hydrolyzing enzymes using amino acid mutant antibodies.
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| Academic Significance and Societal Importance of the Research Achievements |
P2X4に対して機能抑制効果のある分子は「痛み抑制分子」として、現在、世界に2000万人以上も存在する「神経障害性疼痛」に苦しんでいる患者の救済につながると考えられる。また、抗体に薬剤、酵素、タンパク質などを付加する誘導体化により、ターゲットを拡大する試みも行われている。そこで本研究では我々が調製した抗P2X4抗体を「痛み抑制分子」を付加することにより誘導体化し、P2X4機能抑制による「痛みの抑制」、さらに将来的にヒトをターゲットとした「痛み創薬」が可能になるのではないかと考えた。
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