Researchers from the Hadassah University Medical Center's Department of Bone Marrow Transplantation, jointly with Yale University and BioIncept, an American-based biotechnology company, have discovered that a certain peptide released by a fetus during pregnancy, called a "pre-implantation factor" (PIF) is effective in preventing graft-versus-host disease (GVHD) in mice, following a bone marrow transplant.
Bone marrow transplants, performed to treat severe hematologic malignancies, the researchers explain, "often lead to potentially fatal, acute GVHD, despite attempts at better donor–recipient matching and/or use of immunosuppressive agents."
When a fetus releases PIF during its early stages of development (mainly during the first two trimesters), it enables the rooting of the fetus in its mother's uterus, regulating immune activity and preventing the mother's rejection of the fetus, without harming the mother's immune system. Given PIF's immune regulating properties and its effectiveness in developing maternal tolerance, it could logically have the potential to regulate the immune response in GVHD. In addition, the authors note that synthetic PIF treatment has proven effective in preventing immune attacks in nonpregnant models of autoimmunity.
In this study, the researchers transplanted bone marrow and spleen cells from donors into mice and then treated them with PIF for two weeks. Short-term PIF administration reduced acute GVHD and increased survival for up to four months following a transplant. This effect was coupled with decreased skin inflammation and decreased liver inflammation, as well as reduced colon ulceration--all without interfering with the positive effects of the transplant.
"Overall," the researchers concluded, "our data demonstrate that PIF protects against GVHD long term by reducing both target organ and systemic inflammation and by decreasing oxidative stress." This research joins other studies conducted by the Department of Bone Marrow Transplantation, which demonstrated the effectiveness of the peptide in preventing diabetes and central nervous system inflammation.
Since recent tests in the United States have successfully ruled out any toxic or negative side effects in healthy animals as a result of this peptide treatment, researchers can now take the next step and begin clinical trials in humans. According to Prof. Reuven Or, head of Hadassah's Department of Bone Marrow Transplantation, "In the next few months, Hadassah researchers will focus on preparing for the upcoming clinical trial and making sure we have all necessary documents and approvals in order to begin."