Repurposing of multiple sclerosis (MS) and graft versus host disease (GVHD) therapeutics to inhibit chronic rejection of transplanted organs
More details
Hide details
Transplant Immunology, Houston Methodist Research Institute, Houston, Texas, United States
The Houston Methodist Hospital, Department of Surgery, Houston, Texas, United States
Submission date: 2023-08-07
Final revision date: 2023-08-11
Acceptance date: 2023-08-14
Publication date: 2023-12-29
Corresponding author
Malgorzata Kloc   

Transplant Immunology, Houston Methodist Research Institute, Betner Avenue, 77030, Houston, United States
LW 2023;101(4):305-310
Chronic rejection of transplanted organs is an incurable event in transplantation. Macrophages infiltrating allograft induce vessel occlusion and tissue fibrosis, which over the months-years post-transplantation cause organ failure. Patients require re-transplantation, which is extremely problematic because of the permanent lack of organ donors. Our studies showed that chronic rejection depends on the function of macrophages and the RhoA/ROCK pathway. Genetic (RhoA knockout) or pharmacologic (ROCK inhibitors) interference with the RhoA pathway inhibits macrophage functions and prevents chronic rejection in the rodent transplantation model. Most commercially available RhoA pathway inhibitors are not approved for clinical use. However, we found two compounds: fingolimod (Gilenya, FTY720) and belumosudil (Rezurock), which are clinically approved for relapsing multiple sclerosis (MS) and chronic graft versus host disease (cGVHD), respectively, which also inhibit the RhoA pathway. We tested these two drugs in the rodent transplantation model, and both inhibited chronic rejection. Thus, we proposed to repurpose these drugs for organ transplantation. A clinical trial on the effect of fingolimod in kidney transplant patients is ongoing, and the belumosudil trial is pending.
Journals System - logo
Scroll to top