Drug therapy for the management of radiation-induced hematopoietic and gastrointestinal syndromes

Nuclear technology is widely used in industry, army and medicine (diagnosis, radiotherapy and conditioning for transplants). Circumstances in which high-dose radiation exposure occurs can result in a considerable number of injuries and deaths in the absence of therapeutic intervention. These circumstances may include terrorism, accidents caused by nuclear reactor malfunctions, or radiotherapy accidents involving ionising radiation (IR) overdose. There are also medical cases of high-dose irradiation for the purpose of conditioning the patient for transplantation to treat certain diseases (acquired bone marrow failure, acute myeloblastic leukemia (AML) or hereditary aplastic anemia).
Exposure to high levels of radiation can quickly lead to acute radiation syndrome (ARS), which mainly affects hematological (blood, bone marrow) and gastrointestinal tissues in the hours, days and weeks that follow.
Hematopoietic syndrome (HS) is a major component of ARS. It develops after total body irradiation (TBI) at doses > 1 Gy and is characterized by partial or total destruction of bone marrow stem cells and their environment. The therapeutic management of HS is based on medical treatments using growth factors to stimulate residual hematopoiesis, but these may prove ineffective in cases of severe bone marrow damage. Hematopoietic stem cell transplantation is then the best treatment, but it is invasive, not always feasible due to a lack of donors, and its success rate remains extremely low, particularly due to severe side effects (risk of graft-versus-host disease).
Gastrointestinal syndrome (GIS) develops after a dose > 10 Gy (whole body or localized). It is characterized by weight loss, diarrhea and increased susceptibility to developing bacterial infections leading to septicemia. Death occurs within 5 to 12 days after irradiation. Current management is based solely on symptomatic treatments (antibiotics, anti-diarrhea drugs, anti-emetics).
It is therefore essential to develop new therapeutic methods to treat severely irradiated patients as quickly as possible after radiation exposure and with minimal side effects.
In this project, we propose to develop, through industrial and clinical collaborations, new drug therapies involving the administration of specific molecules to be tested in order to improve hematopoietic and/or intestinal recovery after irradiation.