From discovery science to product development
MirZyme is translating research into the vascular pathways associated with preeclampsia into diagnostic and therapeutic programmes. This work has informed the development of M-PREG®, a UKCA-marked clinical decision support tool that provides clinicians with a three-category traffic-light assessment, and MZe786, an investigational oral small-molecule candidate for preeclampsia.
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Scientific Principles
A number of studies have consistently shown that the imbalance in anti-angiogenic factors is most strongly associated with the clinical signs of preeclampsia and disease severity.
Anti-angiogenic factors such as soluble Flt-1 (sFlt) and soluble endoglin (sEng) are increased prior to the clinical onset of preeclampsia and pregnant animals exposed to high circulating levels of sFlt-1 illicit severe preeclampsia symptoms. Preeclampsia arises due to the loss of vascular endothelial growth factor (VEGF) activiy as a result of the increase of endogenous sFlt-1,
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The Car Analogy
Pregnancy can be seen as a journey in a car. The accelerator is represented by the angiogenic milieu and the brakes are represented by the protective pathways that we have discovered. It is the failure in the braking systems during the journey that causes an imbalance and results in the ‘accelerator’ driving out of control until the system eventually crashes. In this analogy, the system crash manifests itself as preeclampsia.
When the system starts to fail, the detection of a failure in the braking system is represented by our diagnostic test. Our therapeutics provide ways to replace the failing brakes with new brake pads, therefore maintaining system balance and preventing the car from crashing i.e. preventing preeclampsia.
MirZyme has developed ways to identify diagnostics and therapeutics for preeclampsia that target the protective pathways and the networks connecting them.
Learn more about our discoveries
What is preeclampsia?
Preeclampsia is a common condition in pregnancy, which can be life-threatening for both mother and baby in severe cases. It is often difficult to diagnose and hence the term "silent killer". The symptoms may include high blood pressure and multiple organ damage in the mother leading to premature delivery of the baby. It is a massive public health burden, costing billion dollars and affecting nearly 10% of all pregnancies.
It is without a medical cure. The absolute risk reduction with low-dose aspirin is only 2-5% and this is ineffective in significantly preventing preeclampsia. In the UK alone, 40,000 pregnant women are diagnosed with preeclampsia, costing the NHS over £600 million per year. Globally, it affects millions of pregnant women each year and is responsible for up to one in four of small for gestational age babies or fetal growth restriction (FGR) cases. It also accounts for up to one in five of all pre-term births.
Every minute, a live is lost to preeclampsia. This amounts to over 1,500 daily deaths of mothers and babies. Just think, peeclampsia affects more than twice the population of London, every year.
Preeclampsia can have long-term adverse effects on the mother and the baby, thus increasing the risk of developing chronic diseases later in life. We have shown that preeclampsia is a ‘double hit’ vascular disease with defects in the protective pathways of heme oxygenase-1 (Hmox1) and Vascular Endothelial Growth Factor (VEGF) signalling.
High risk factors for preeclampsia identified during booking appointment
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Hypertensive disease during a previous pregnancy
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Chronic kidney disease
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Autoimmune disease such as systemic lupus erythematosus or antiphospholipid syndrome
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Type 1 or type 2 diabetes
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Chronic hypertension
Moderate risk factors for preeclampsia identified during booking appointment
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First pregnancy
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More than 40 years old
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Pregnancy interval of more than 10 years
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Body mass index of 35 kg/m2 or more at first visit
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Family history of preeclampsia
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Multiple pregnancy
What is FGR?
Globally, an estimated 20 million infants are born annually with low birthweight (<2500 g). The classification of small for gestational age was defined by a 1995 WHO expert committee as infants below the 10th percentile of birth-weight-for-gestational-age Fetal Growth Restriction (FGR). It is a condition in which a baby’s growth slows or stops during pregnancy. FGR can be caused by any aberration in the normal biological processes occurring during pregnancy and have adverse effects on the growth of the fetus. Preterm and preeclamptic infants are at higher risk of FGR compared to full-term and healthy infants. More importantly, FGR infants are 7 times more likely to die prematurely.
The current diagnosis of FGR is based on discrepancies between actual and expected sonographic biometric measurements for a given gestational age. In many Western countries, primary care for suspected FGR are serial fundal height assessments to monitor the fetuses.
If FGR is suspected, patients are asked to have:
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Fetal ultrasounds to estimate the fetal weight
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Doppler ultrasound to check the blood flow to the placenta and through the umbilical cord to the baby. A fetus with FGR will have decreased blood flow.