Preeclampsia affects 2% to 8% of pregnancies. It manifests itself through the appearance of symptoms in the mother as early as 20 weeks' amenorrhea, including hypertension, proteinuria (presence of protein in the urine) and damage to the maternal vascular system affecting various organs, including the heart and brain.
To date, there is no treatment to alleviate these symptoms or cure the condition, with the exception of termination of pregnancy, which can lead to premature delivery. Among the causes of preeclampsia, the genetic mutation of the STOX1 transcription factor has been identified.
In this context, our research team used a gravid mouse model carrying this mutation to study the mechanisms of the pathology and explore new therapeutic avenues based on inhibition of the PROKR2 receptor for prokineticins, a family of proteins involved in the development of the placenta.
The STOX1 heterozygous pregnant mouse model was used to generate two distinct forms of preeclampsia. The first, representative of preeclampsia of placenta origin (STOX1 heterozygous fetus), and the second representative of preeclampsia of maternal origin (normal fetus growing in a preeclamptic environment). The researchers tested the effects of PKRA, a PROKR2 antagonist, on the alleviation of symptoms in both forms of preeclampsia. They observed that this treatment reduced hypertension and proteinuria in both forms. Moreover, its efficacy was more marked when preeclampsia was of maternal origin. Finally, they demonstrated
in vitro that treatment with PKRA attenuated the damage to vascular integrity induced by overexpression of the STOX1 gene.
This study proposes a new treatment for preeclampsia based on inhibition of the PROKR2 receptor, offering prospects for treating the vascular alterations associated with this pathology.
Fundings
Inserm Transfert
Collaboration
- Cochin Institute
- CEA Saclay
- University of Melbourne