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Kurzfassung

Pre-eclampsia is caused by an imbalance between the pro-angiogenic factors VEGF and PIGF and the anti-angiogenic factor sFlt-1, because sFlt-1 binds both factors. This binding leads to the inactivation of VEGF and PIGF. The present invention relates to a method by which sFlt-1 is eliminated from blood in an apheresis procedure by passing the blood over a column containing immobilised moVEGF165 or scVEGF165. Simultaneously with sFlt-1 binding, sFlt-1-bound VEGF and PIGF are released so that the angiogenic balance, essential for fetal development, is restored after the return of the two pro-angiogenic factors.

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Hintergrund

Preeclampsia is still a threat to pregnant women’s health world-wide and in industrialized countries the most common cause of prematurity, including all potential complications of preterm delivery and its sequelae later in life. In the pathogenesis of preeclampsia, increased expression of soluble FMS-like tyosine kinase 1 (sFlt-1) acts as an antagonist by scavenging and neutralizing the pro-angiogenic vascular endothelial growth factor (VEGF) and placental growth factor (PIGF). The resulting angiogenic imbalance may progress to enothelial dysfunction and thrombotic microangiopathy, manifesting with seizures, stroke, or multiorgan failure. Effective therapeutic and prophylactic measures are lacking, limiting interventional options to premature termination of pregnancy. Thus, therapies for preeclampsia are still an unmet and urging medical need. 

 

 

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Lösung

The underlying invention aims at using an apheresis based approach with recombinant monomeric (moVEGF¹⁶⁵) or two single-chain dimers of VEGF¹⁶⁵ (scVEGF¹⁶⁵). Both compounds enhance binding affinity to sFlt-1 and efficiently reduce or eliminate sFlt-1 levels from plasma of preclampsia affected women. Compared to approaches based on antibodies in the art, the use of both compounds as a ligand has the additional effect that bound VEGF and PIGF are displaced and released from sFlt-1. Overall, this minimizes the risk of life-threatening conditions and, in particular, restores uterine vascularization and establishment of uteroplacental circulation.  

 

 

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Vorteile

• Restoring the angiogenic balance by displacing endogenous VEGF and PlGF from its binding to sFlt-1
• moVEGF¹⁶⁵ and scVEGF¹⁶⁵ have a higher affinity to sFlt-1 as compared to antibodies
• Efficient elemination of sFlt-1 from plasma by moVEGF¹⁶⁵
  and scVEGF¹⁶⁵
  

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Anwendungsbereiche

There is strong interest in novel approaches with regard to extracorporeal therapies for preeclampsia. So far only one company is in the process of developing an antibody-based approach of sFlt-1 apheresis, which is less efficient as compared to this VEGF-based apheresis system. Specifically, the efficient liberation of endogenous VEGF and PlGF is an advantage of this novel approach.

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Service

Before rolling out to clinical studies in pregnancies with preeclampsia, toxicity and compatibility, e.g. the safety of endogenous VEGF- and PlGF-release for mother and fetus, has to be tested in vivo. Finally, pivotal clinical trials comparing this novel strategy to the state-of-the-art at this future time point will be needed before approval of this novel medical device.