USE OF SSRI ALONE OR IN COMBINATION WITH GROWTH FACTORS FOR TREATING CYTOPENIA

Following acute stresses like chemotherapy or radiation, the hematopoietic system quickly adapts by a process termed “emergency” or “stress” hematopoiesis. In erythroid progenitors, the researchers recently identified a functional cellautonomous serotonergic network with pro-survival and proliferative functions (Cell Reports 2019). Pharmacologic restoration of serotonin levels using selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, a common antidepressant, can rescue the anemic phenotype in mice models. In this project, the team has shown that the serotonergic system could be a valuable therapeutic target in radiation or chemotherapy-induced cytopenia, alone and in cooperation with known hematopoietic growth factors, such as G-CSF. Particularly, fluoxetine alone or in combination with G-CSF showed an additive effect on the recovery of the three myeloid lineages and on overall survival of mice following sub-lethal irradiation. This new combination of drugs offers interesting avenues to fasten hematopoietic recovery of cytopenia thereby decreasing the risk of complications for patients during aplasia.

Applications:

• Chemotherapy or radiationinduced cytopenia
• Bone marrow failure
• Reduction of the hospitalization time after chemo- or radiotherapy

Competitive advantages:

• Unique simultaneous action of SSRIs on the three myeloid lineages, showing faster recovery after cytopenia, saving at least 2 days of hospitalization
• Additional synergistic effect of SSRI with G-CSF
• Lower cost of SSRIs compared to the current treatment (mainly G-CSF alone)

Keywords: Cytopenia, Serotonergic system, Hematopoiesis, Aplasia, Serotonin reuptake inhibitors (SSRI), Bone marrow failure