Development of immunosuppressive therapy with teprenone to reduce the severity of aGVHD after HSCT

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K12751
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90140:Medical technology assessment-related
• Research Institution: Okayama University
• Principal Investigator: Fujii Keiko 岡山大学, 大学病院, 助教 (40728606)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 造血幹細胞移植 / 移植片対宿主病

Outline of Final Research Achievements

A randomized clinical trial was conducted to evaluate the efficacy of Teprenone in combination with conventional GVHD prophylaxis for the prevention of severe aGVHD after HSCT. The intervention consisted of oral administration of teprenone (50 mg three times a day) for 21 days from the start of pre-transplantation treatment, while the usual GVHD prophylaxis was performed. A total of 40 patients were included, 21 in the control group and 19 in the teprenone group. 9 patients (6 in the control group and 3 in the teprenone group) had severe aGVHD, but the incidence was not significantly different between the two groups. there were no differences in expression of oxidative stress markers such as Trx-1. There was a significant increase in IL-33 in patients with severe GVHD, and further studies are needed to determine whether this is a useful biomarker for early detection.

Free Research Field

血液・腫瘍内科

Academic Significance and Societal Importance of the Research Achievements

免疫抑制効果とは無関係な作用機序（細胞保護等の効果）でGVHDのリスクを下げる薬剤については、臨床上で開発が全くおこなわれていないのが現状である。テプレノンの主成分であるGeranylgeranylacetone(GGA)は胃粘膜のほか、小腸、肝臓、心臓、腎臓、脳など様々な組織でHSP70に加え、Trx-1を誘導しGVHDにおいても細胞保護が期待できる可能性がある。なによりもテプレノンは副作用が少なく汎用性が高いものであり、効果が認められた場合早期に臨床応用ができ移植医療へ貢献することができる可能性がある。この度は安全性が認められている範囲の投与量で試験を行った。バイオマーカーは期待される。