New Videos: Downton Abbey, preeclampsia, and the search for a cure using stem cells

(Downton Abbey Spoiler Alert: skip ahead to the video if you haven’t seen Season 3!)

If you’re one of the estimated 10 million devoted Downton Abbey TV viewers, then you most probably have heard of the word “preeclampsia.” In a heart-wrenching episode from season 3 of the early 20th century British drama, one of the characters dies while giving birth due to the complications of preeclampsia.

A fan myself, I too watched in shock as the plot unfolded. But I was at least comforted by the thought that surely this disease no longer has tragic outcomes today in the early 21st century. Boy was I wrong. As CIRM-grantee Mana Parast pointed out during her Spotlight on Disease presentation to the CIRM Governing Board two weeks ago (now viewable on our website), preeclampsia and related disorders are still a widespread problem for expecting mothers:

“They complicate 5-8% of all pregnancies worldwide, and they cause multiple maternal and neonatal complications. So in fact preeclampsia is the leading cause of maternal mortality in the developed world. It’s also the leading cause of fetal growth restriction and there’s no cure … except to deliver the baby. In fact preeclampsia is the number one cause of induced preterm delivery in the U.S.”

Preeclampsia is often called “the Silent Killer” because the symptoms often arise suddenly in the second half of pregnancy. The main noticeable symptoms for the expectant mother are high blood pressure and high protein levels in the urine, or proteinuria. Silvia Michelazzi, a preeclampsia survivor, shared with the Board her daughter’s birth story:

“My pregnancy, I was thinking, was going well. I knew Mia was a little bit smaller than average but that was pretty much it. But at a doctor’s appointment, it was found out that I had high blood pressure and proteinuria and I was rushed to the hospital and the baby was delivered 48 hours later [at 29 weeks] because there’s really nothing else to do but delivery the baby. I can’t tell you how hard it was to see the baby so small. It turned out she weighed 2 pounds 8 ounces.”

Mia, now three, spent two months in the neonatal intensive care unit but is now doing remarkably well. But some babies aren’t so lucky. They can have intestinal problems, bleeding in their brain, retinopathy of prematurity (a condition that can lead to blindness), and the list goes on. Even when they survive the neonatal stage they still have an increased risk of heart disease and diabetes over the course of their lives. And all of these scary, sometimes fatal complications are basically due to, as Dr. Parast puts it, “just having a bad placenta.”

The placenta is a transient organ that only appears during pregnancy and is critical for exchange of food, blood and oxygen between the mother and fetus. Dr. Parast, a perinatal pathologist at UC San Diego, studies the development of the placenta with the ultimate hope of finding treatments for preeclampsia. If you imagine the early embryo as a tiny hollow ball of cells, it’s the outer cells called trophoblasts that ultimately form the placenta while a clump of cells inside the hollow “ball” go on to form the fetus.

Examination of a preeclamptic placenta after delivery shows that preeclampsia is a disease marked by a malfunction in trophoblast maturation leading to abnormal placenta development. The aim of Dr. Parast’s team is to mimic preeclampsia in the lab but it’s been a tricky disease to model because preeclampsia is unique to primates so experiments in mice is not an option. Instead, with the help of CIRM-funding, Parast’s lab is embarking on a project to bank tissue from preeclamptic placentas and derive trophoblasts using the induced pluripotent stem cell (iPS) technique. With these iPS-derived trophoblasts in hand, the team can screen for drugs that restore proper trophoblast maturation and placental development.

And in a strange twist that you usually only see on a TV show – it turns out that Dr. Matteo Moretto-Zito, a researcher in Parast’s lab, is the father of little Mia. Moretto-Zito had joined the lab shortly before his wife Silvia was diagnosed with preclampsia. He also spoke to the Board and had this to say about his unique perspective:

“I consider myself extremely lucky for two reasons: number one, Mia’s story ended up really well so that is great and reason number two, because I am part of a team that can make a difference.”

Here’s to hoping that Matteo and the entire Parast team make a difference and find a treatment to end preeclampsia complications for future moms and babies.

A Second Chance for a Spinal Cord Injury Trial, and a Powerful Reminder from Patient Advocates

Yesterday’s meeting of our governing Board was important for a number of reasons. First, the Board voted to invest some $32 million to try and get two promising projects into clinical trials – more on that in a minute – and also to try and attract some world-class researchers to California through our Research Leadership awards. It was also the first Board meeting for our new President, C. Randal Mills, Ph.D.

However, for me one of the most important parts of it was that it offered patient advocates a chance to come and talk to the Board directly, to share with them their hopes for stem cell research, and their needs in battling disabling conditions.

Yesterday a mother, Silvia Michelazzi, who suffered preeclampsia during her pregnancy and almost lost her child talked about the need for research to find better ways of preventing this deadly condition. Silvia’s daughter was born at 29 weeks and spent the first couple of months of life in a hospital neonatal intensive care unit.

One of the researchers we are funding, Dr. Mana Parast of UC San Diego, is doing some fascinating work in using iPS cells to better understand how preeclampsia works, and hopefully to find better ways of preventing it or treating it when it’s detected. We’ll be posting video of both talks in the next few weeks.

Earlier a group of individuals who have Parkinson’s disease talked to the Board about what it is like to live with that disease, to slowly lose control over their bodies and know that it was only going to get worse. They made a strong plea for more funding for stem cell research into this area.

To hear people like this speak is a powerful reminder of why we do this work; it puts a human face on the need for more research into so many areas, and why we need to do all that we can to accelerate that research, to find new treatments and cures.

Too often patients are left out of the discussion when it comes to funding research. At the stem cell agency we invite them into the room and welcome hearing from them. It’s not always easy to listen to what they have to say, particularly as we know some research is at an early stage of development and we won’t always be able to do what they want us to. But those voices are an important part of what this agency is all about. We were created by the people of California, so it’s important that the people feel they can come and talk to us any time they want.

From a business perspective yesterday’s meeting was very productive. The Board voted to invest $14.3 million in Asterias Biotherapeutics to move a stem cell therapy for spinal cord injury into clinical trials. This is the second time this approach will have been tried. The first was with Geron in 2010 and that trial, even though it ended earlier than expected because of financial reasons, showed the approach appears to be safe. Asterias is going to take it to the next level.

The other big award was $5.6 million to John Zaia at the City of Hope near Los Angeles to move his work in finding a treatment for HIV/AIDS into clinical trials.

Both are part of our Strategic Partnership program that requires them to provide matching funds for this work.

You can read all about those awards and the Research Leadership ones too in a news release we issued after the meeting.

kevin mccormack