Elucidating the pathogenesis of childhood-onset pulmonary hypertension through multifaceted pathological investigation based on deep learning

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17623
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Hokkaido University
• Principal Investigator: Nagai Ayako 北海道大学, 大学病院, 医員 (10622160)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肺動脈性肺高血圧症

Outline of Final Research Achievements

First, drug X-encapsulated nanocapsules were fabricated to efficiently encapsulate drug candidate X, a novel therapeutic agent for pulmonary arterial hypertension (PAH), into pulmonary artery smooth muscle cells. Compared to drug X administered alone, the drug X-encapsulated nanocapsules significantly inhibited the proliferation of pulmonary arterial smooth muscle cells of PAH patients. Next, a rat model of PAH was created. The model rats were divided into three groups: a group treated with Drug X-included nanocapsules, a control group treated with empty nanocapsules, and a non-treated group, and were examined by cardiac catheterization. The results showed that right ventricular pressure was significantly decreased and Fulton index was significantly improved in the group treated with the drug-X-encapsulated nanocapsules. The investigators plan to evaluate the pulmonary pathology in each group to further validate the efficacy of Drug X-encapsulated nanocapsules as a treatment for PAH.

Free Research Field

小児循環器学

Academic Significance and Societal Importance of the Research Achievements

近年、PAHに対して既存の系統とは別の介入経路を見出そうとする研究が、国内外で散見されているが、その応用については、いまだ多数のハードルがあり、実現は困難な状況である。本研究が目指す、既存の治療薬の介入経路とは異なるメカニズムでPAHの改善に寄与し、かつナノカプセルにより薬理効果を純粋に活用する研究は国内外ともに皆無である。本研究はPAHの新たな治療法の開発に寄与するものであり、また、これまでに確立されているPAH治療薬の介入経路とは全く異なる経路からのアプローチであるため、既知の治療薬との併用による、治療効果のさらなる向上も期待できる。