2023 Fiscal Year Final Research Report
Novel protocols of inhaled GM-CSF therapy for smoker patients with pulmonary alveolar proteinosis
| Project/Area Number |
20H03686
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TAZAWA Ryushi 東京医科歯科大学, 学生支援・保健管理機構, 教授 (70301041)
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| Co-Investigator(Kenkyū-buntansha) |
石井 晴之 杏林大学, 医学部, 教授 (30406970)
中田 光 新潟大学, 医歯学総合病院, 特任教授 (80207802)
田中 崇裕 新潟大学, 医歯学総合病院, 助教 (70455400)
小松崎 恵子 東京医科歯科大学, 職員健康管理室, 助教 (50867306)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | GM-CSF / 抗GM-CSF抗体 / GM-CSF吸入治療 / 肺胞蛋白症 / リツキシマブ |
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| Outline of Final Research Achievements |
We conducted the following studies on granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation therapy for autoimmune pulmonary alveolar proteinosis (aPAP), which Japanese authority recently approved. A search for positive cases in other diffuse lung diseases revealed a few positive cases in patients with hypersensitivity pneumonitis. We attempted to rhGM-CSF inhalation treatment in combination with rituximab to suppress anti-GM-CSF antibodies in four cynomolgus monkeys at a fully AAALAC certified facility under the approval of the Animal Experiment Ethics Committees. The animals completed treatment without any serious side effects, and the antibody production was suppressed at the initial stage of the inhalation. To consider an efficient inhalation method, we created a mathematical model for the pharmacokinetics of GM-CSF from the respiratory tract to the bloodstream, suggesting the importance of drug deposition in the bronchi and advection to the alveoli.
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| Free Research Field |
呼吸器内科
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| Academic Significance and Societal Importance of the Research Achievements |
aPAPに対するGM-CSF吸入製剤は本年薬機法による製造販売承認がおりて今後実地臨床での使用が進められるが、その際に大きく参考となる研究成果が得られた。診断に有用な抗GM-CSF抗体について知見が得られ、GM-CSF気道投与とリツキサン静脈注射の併用の可能性がカニクイザルで検討され、効率のよい吸入方法を考えるため、過去の非臨床試験データを基盤に、分子量の大きいGM-CSF製剤の気道～血中への薬物動態の数理モデルが作成され、1回換気量や呼吸回数が吸気の薬剤濃度・滞留時間に影響することが示唆された。
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