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Profile: Lynda Harris and promise for preterm births

Profile: Lynda Harris and promise for preterm births - 5 June 2013

BBSRC-funded team wow the OneStart competition with the first novel drug carriers to safely target the placenta.

How does it feel to be Runner-up?

We were delighted. We didn't think we'd get this far in the competition because it is primarily for developing businesses with a product to commercialise and stimulating biotechnologists to be entrepreneurs. We're at early stages of research so we didn't think we'd get into the final.

The LipoPep team l-r: Anna King, Dr Lynda Harris, Natalie Cureton.
The LipoPep team l-r: Anna King, Dr Lynda Harris, Natalie Cureton.

How did your business plan come together?

It was really down to my two PhD students Anna King and Natalie Cureton, who are co-supervised by Professor John Aplin and Professor Nicolla Tirelli at The University of Manchester. They entered a similar competition, Venture Further, run by the university and won the £10K prize in the technology category. They heard about this European competition, OneStart, and it went really well from the first round to the semi and on to final, developing more detailed business plans at each stage on how you would commercialise the product (LipoPep).

Describe your winning entry…

The idea was building on the research of my two PhD students, Anna King and Natalie Cureton, to synthesize liposomes, which are like small bubbles that can be modified to display the placental-homing peptides on their surface. This creates a little drug carrier and when you introduce it intravenously it binds only to the placenta, and doesn't accumulate in any other organs so you don't get off-target side effects from the drugs you are administering.

It's an idea developed originally for delivering chemotherapy to tumours. Because cancer drugs are toxic and you don't want them accumulating around the body, this method of targeting reduces the side effects as well as the amount of drug you need. Lots of companies aren't interested in developing drugs for pregnant women because of the high risk, so I thought if we had a way to target drugs directly to the placenta that would reduce the risk in pregnancy.

How do you make drugs only target the placenta?

The drug can be packaged inside the liposome, and the homing peptides [short chains of amino acids that coat the liposome], bind selectively to the placental surface. And depending on the properties of the liposome it can release the drug at the placental surface or be taken up by the placenta.

How did BBSRC funding lead to this?

Placental-specific homing peptide (green) binding to human placenta in vitro. Image: Natalie Cureton
Placental-specific homing peptide (green) binding to human placenta in vitro. Image: Natalie Cureton

I'm supported by a BBSRC David Phillips Fellowship, which funds me to identify specific homing peptides that bind to the surface of the placenta. I did the initial work screening for the peptides, and both my PhD students are taking that work further by building different carriers and testing different drugs in animal models.

One of my PhD students, Natalie Cureton, is on a BBSRC-funded Doctoral Training Programme (DTP) and she is designing novel nanocarriers to target drug delivery to the placenta, trying different formulations of liposome and different peptides to find the ones that work best. This broadens the scope of the research and allows us to do more in the time available.

Why target the placenta?

A poorly functioning placenta is the cause of many pregnancy problems, so by targeting the placenta we are treating the problem rather than treating the symptoms. You can either give drugs that increase blood flow into the uterus and placenta, to supply more nutrients and oxygen to the tissue, or you can give drugs that encourage placental growth, to increase the surface area and speed of nutrient uptake.

We know from evidence from a lot of animal studies – mice, rats and sheep – that either increasing placental size or function or increasing blood flow improves outcomes for the baby. And this can relieve maternal symptoms too.

What kind of conditions could this be used for?

The two main serious pregnant complications are pre-eclampsia – when the mother's blood pressure gets dangerously high and her kidneys start to fail – and also foetal growth restriction when the baby is just not growing properly.

How many women suffer from these kinds of complications?

Around 10% of pregnant women will have serious pregnancy complications including these. But at the moment you can't treat them – all you can do is monitor the women and deliver the baby early. So this would be the first treatment to improve placental function. And because the scanning and biomarker technology has got better, we can identify women earlier who are at risk of developing these conditions.

And what is the cost of these conditions?

The total cost of neonatal intensive care costs for preterm birth to NHS is £2.9Bn a year (ref 1), but this does not include the cost of the mother's stay in hospital, the extra appointments she needs or the costs of a complex delivery. And in the US the figure cited is US$26Bn a year (ref 2).

What's the next step?

We want to complete pre-clinical tests and development of the liposome carrier and carry out more detailed studies in mice to see how well we can improve placental growth and function. At the moment we know the liposomes bind to human placenta in vitro, and we also know if we inject it into mice it works in vivo. We've delivered fluorescent dyes so far, so we know the drug can get to the right place – now we need to try the drug itself.

In the organism: placental-specific homing peptides (green) binding to mouse placenta in vivo. Image: Lynda Harris
In the organism: placental-specific homing peptides (green) binding to mouse placenta in vivo. Image: Lynda Harris

Candidate drugs include the growth factor IGF-II and the vasodilator sildenafil citrate. In the next three years we want to get as much animal testing done as possible, then we can start to think about early phase human clinical trials.

How much might the pregnancy drug market be worth?

We had to work this out for the pitch. There is only one other similar drug on the market which is a cancer drug delivered in a liposome called Doxil, and it generated US$400M in 2011. And it's a similar formulation so our production costs would be similar. If we treat 10% of all pregnant women then we have a big market with no competitors.


Are there unique safety challenges working towards a pregnancy drug?

I think we're going to have to test it very well, but there are women who have repeated pregnancy problems and their offspring have a very low chance of survival, and those women may be more willing to try anything if it helps their baby survive. Or if their offspring has a likely poor outcome, then maybe they will contribute to a clinical trial. And we have various specialist research midwives in Manchester who are very good at recruiting women for trials, so I hope we'll be able to get enough people interested and involved.

What inspired you to look at this field?

I started with in interest in human biology and did a degree in Pathobiology, which is basically biomedical science, then did a PhD in vascular biology. And then I accepted a post-doc up in Manchester looking at how the placenta interacts with blood vessels in the uterus – that got me interested in the placenta.

Then it became evident there was no safe way of delivering drugs to pregnant women. That seemed to be a big gap. When I found out that it was possible to target delivery of drugs to tumours, I thought that this technology would work well for the placenta, because you can consider placenta as a big tumour. That's when I applied for the David Phillips Fellowship to do the screening for novel peptides that bind to the placenta.

When did you start DP Fellowship?

I started that in October 2010 and spent first year in big cancer lab in the US, working with Professor Erkki Ruoslahti's at the Sanford Burnham Medical Research Institute, California. It was there that I did the screening for placental peptides and learnt their technology.

Dr Harris in her lab in the US.
Dr Harris in the Ruoslahti lab in the US.

What was working in the US like?

The US was a great experience – it was a big lab with lots of funding, the average age was mid-30s so quite a mature environment with people with specialised knowledge who were really excited about science.

How was it different to working in the UK?

The main difference was people had more responsibility to get on with it – you had more of a free rein to take the research in the direction you want it to go, as long as it's heading towards the major goal. I wouldn't say it was a better system, just different. My work was a major success and I came back with a lot more data than I thought I would and and achieved more than I anticipated. But coming back in UK in November after California was a bit of a shock to the system!

How much of a difference will the £10K prize make?

With the £10K we can get more in vivo animal work done so it all contributes. It's a case of just cracking on with the drug delivery experiments, so this will help us progress more quickly.

Does the visibility of winning such a prize make a difference?

Yes definitely. It helps raise the profile and awareness of the problem. People don't know much about prenatal health as it's not seen as a priority area. People think women have been having babies for years and there's no need to optimise the process, but there is more and more evidence that if you are born too small or early you have poorer health in later life. So if you can encourage healthy development of baby, they are more likely to have better health in later life. It's a long-term money saving exercise for the NHS and better for the life of the child and mother.

When did you realise you wanted to go into science?

I've always been interested in science and human biology and enjoyed the research part of my undergraduate degree. And I quite like the idea of developing something myself and making a contribution to society or changing clinical practice. I like the way that research allows you to be creative and free thinking.

References

  1. Simple test will help predict and prevent premature births
  2. Preterm Births Cost U.S. $26 Billion a Year