September 24, 2020
Keio University School of Medicine
A research team from the Department of Ophthalmology, Keio University School of Medicine, including Professor Kazuo Tsubota, Project Associate Professor Yoko Ogawa, Mio Yamane (at the time of research: Doctoral Programs, Graduate School of Medicine), Mari Sato (4th year, Doctoral Programs, Graduate School of Medicine), and Project Lecturer Eisuke Shimizu, has discovered that cellular senescence is involved in the pathogenesis of chronic graft-versus-host disease (cGVHD), based on experiments using a cGVHD mouse model and findings from human cases.
Senescent cells are known to promote chronic inflammation by secreting senescence-associated secretory phenotype (SASP) factors. In this study, the researchers discovered an upregulation of major SASP factors and accelerated cellular senescence, primarily in the lacrimal glands of cGVHD mouse models and human cGVHD cases. This led them to the idea that ABT-263 (Navitoclax), a senolytic agent, could be effective in treating ocular cGVHD. Administration of ABT-263 to the cGVHD mouse model suppressed the accumulation of senescent cells, decreased the expression of SASP factors, and showed an inhibitory effect on the pathology of ocular cGVHD.
Bone marrow transplantation is widely performed as a curative treatment for hematological malignancies, but cGVHD as a late complication has been a major risk. The results of this study indicate that senolytic agents could become a therapeutic option for ocular cGVHD. These agents are also believed to have the potential to suppress systemic cGVHD, a possibility that will be explored in future research.
These research findings were published in the scientific journal "The FASEB Journal" on July 3, 2020 (Eastern Time).
For the full press release, please see below.