Development of novel therapeutic agent for pachydermoperiostosis (PDP) using iPS cells derived from patients with PDP

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08649
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kyoto University
• Principal Investigator: Nomura Takashi 京都大学, 医学研究科, 特定准教授 (60346054)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: pachydermoperiostosis / prostaglandin / SLCO2A1 / iPSC

Outline of Final Research Achievements

Pachydermoperiostosis (PDP) is a genetic disorder characterized by clubbed fingers, periosteal thickening (periostosis), and skin thickening (pachyderma). The cause is thought to be PGE2 excess caused by the deficiency of PGDH or SLOCO2A ; COX inhibitors relieve symptoms. However, SLCO2A1 deficiency often precludes the use of COX inhibitors because of concomitant gastrointestinal symptoms. In this study, we focused on SLCO2A1-type PDP and aimed to identify therapeutic agents other than COX inhibitors. SLCO2A1-deficient cells are useful for this purpose. In this study, we established at least one cell-line of iPS cells derived from a patient with complete PDP. This made it possible to analyze the function of SLCO2A1 and the effects of its deficiency in vitro.

Free Research Field

Immunology

Academic Significance and Societal Importance of the Research Achievements

肥厚性皮膚骨膜症(PDP)は、ばち指、骨膜肥厚、皮膚肥厚、骨髄線維症等の多彩な症状を呈する。これらの症状はPDPに限らず肺疾患や、特に原因のない患者でも見られることがある。本研究成果は、これらの特発性疾患の原因解明につながる可能性があり、学術的意義が大きい。また本研究は、高熱、全身倦怠感、皮膚肥厚による機能的整容的障害、骨膜肥厚による関節痛や運動制限、熱中症等々、PDP患者の生活上の制限を改善することにつながることから、社会的経済的意義も大きいと考える。