a1m_blogpost1


Pre-eclampsia continues to be a complex health problem and has attracted many schools of thought, so it’s not surprising it’s become known as ‘the disease of theories’.

As one of the leading causes for mothers and unborn babies to become ill or die during pregnancy, it’s a vast global health problem.


The basics

Pre-eclampsia usually affects women in the second half of pregnancy when they start having high blood pressure and protein in their urine (also known as ‘proteinuria’).

But while the clinical symptoms unveil themselves after the 20th week of pregnancy, the problem really starts at the beginning of the pregnancy.

The condition is thought to be caused by problems in the development of the placenta – the organ that connects mother and baby across the womb and helps food and oxygen pass from mother to baby, and waste pass back.

“A typical pregnancy is 40 weeks,” explains Professor Stefan Hansson, head of clinical research and development at A1M Pharma, “In the beginning the egg is fertilised and starts to divide then ends up in the uterus where it sinks into the uterus wall.

“Immediately cells from this begin growing into the uterus, establishing the ‘uterus-placenta’ connection. But in pre-eclampsia something goes wrong in this part of the process resulting in a weaker connection and a reduced blood flow into the placenta.”

Worldwide, pre-eclampsia affects two to eight per cent of all pregnancies. If it isn’t treated it goes on to become eclampsia – a condition that causes pregnant women to have seizures.

Though eclampsia is rare in the developed world, it still affects about one to three per cent of those with pre-eclampsia in the developing world. And, alongside other diseases linked to high blood pressure, pre-eclampsia causes one in ten deaths of pregnant mothers in Africa and Asia one in four of those in Latin America.

Currently the only treatment for the condition is to deliver the baby early, and so pre-eclampsia also causes 15 per cent of all premature births.

Symptoms

There are no signs of the condition when pre-eclampsia develops at the start of pregnancy. But during the second half of pregnancy doctors check blood pressure and use urine tests to check for warning signs of high blood pressure and proteinuria.

Other symptoms of pre-eclampsia that mothers might spot can include: headaches, problems with vision, nausea, pain in the stomach, back or shoulder, sudden weight gain, shortness of breath or swelling of the face, hands, ankles and feet.

We also know that pre-eclampsia is more common in women who are pregnant for the first time, those who have had it in previous pregnancies, mothers expecting twins and pregnant women who already have high blood pressure, or who are obese, have diabetes or kidney diseases.

How does it develop?

Some pre-eclampsia theories – like the mother’s diet and environment – are seemingly simple, while others explore complex science about the mother’s and baby’s immune systems or certain genes.

Delving deeper into the faults in the formation of the placenta, A1M Pharma scientists believe that these errors stem from the baby producing extra haemoglobin – a part of the blood that carries oxygen – because the weaker connection in the placenta means less oxygen gets to the baby.

“The placenta is built badly in first three months of pregnancy and this means that there’s a shortage of oxygen for the baby,” describes Professor Bo Åkerström, A1M Pharma’s head of pre-clinical science.

“We have shown that the baby produces more haemoglobin, possibly to try to get more oxygen from the mother.”

But too much haemoglobin is toxic and causes oxygen radicals to form. These faulty types of oxygen attack the placenta and blood vessels eventually leaking into the mother’s system and attacking her blood vessels and organs.

“Extra haemoglobin and oxygen radicals damage the blood vessel walls, causing them to narrow so that blood pressure increases,” explains Professor Hansson.

“You get problems in all organs, but the kidneys are the first to signal this with the proteinuria. This is because they take in more blood, and therefore more toxic substances, when they filter it.”

The role of A1M

Within this chaos our scientists found a clue about how to tackle pre-eclampsia. They saw that a protein called alpha-1-microglobulin, or A1M, was found in high levels around the site of the damage.

“We know that women with pre-eclampsia have higher levels of A1M than in normal pregnancies,” explains Professor Åkerström.

“Naturally all of our cells are surrounded by a solution that contains A1M and when cells break this flows in to help fix them. A1M picks up molecules in its basket-like structure – particularly oxygen radicals and the toxic parts of haemoglobin – then takes them to the kidney to be filtered out. It also repairs the damage caused by haemoglobin and oxygen radicals in the blood vessels and kidneys, so we think A1M will work against pre-eclampsia.”

Six years ago they began researching whether giving extra A1M in pre-eclampsia might stop the condition.

Right now this research is still being done in animals but shows promise, and they think it may become an important tool to target the very faults that cause pre-eclampsia.