Placental Gene Transfer of IGF-1 Corrects Fetal Growth Restriction

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read the abstract:  Placental Gene Transfer of IGF-1 Corrects Fetal Growth Restriction

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Alix Boyle: Hi, this is Alix Boyle, reporting for OBGYN.net. I am here at the SMFM meeting in San Francisco 2007. I am here today with Dr. Ursula Harkness from the Mountain Area Health Education Center in Ashville, North Carolina. Tell us about your research.

Ursula Harkness, MD: I am excited to present our research today. This is work that was done with my colleagues at the University of Cincinnati, in Cincinnati Children’s Hospital. Basically we know that intrauterine growth restriction is a major cause of perinatal morbidity and mortality, but we have no treatment at this time. What we looked at was testing in a rat model of placental insufficiency, attempting treatment with placental gene therapy with IGF-1.

Alix Boyle: That sounds really interesting. What were the results of your research?

Ursula Harkness, MD: We were able to correct the growth restriction. Our animals that were made growth restricted by ligating the uterine arteries were 27 percent smaller than the control animals, and we were able to correct that growth disturbance in a dose dependent fashion using two different doses of IGF-1 into the placenta.

We were also looking at not only the birth weight but the post-natal growth of these animals, and the growth restricted animals remained small. But again, the IGF-1 treatment into the placenta with the gene therapy was able to correct post-natal growth disturbance as well.

Alix Boyle: So what does this mean for the future? Are we going to see this type of treatment in humans?

Ursula Harkness, MD: I think we have a long way to go. There are a lot of different areas we need to look at. We did spend some time looking at the safety of the transfer of the gene therapy to both the fetus and the mother. Certainly we did not see any transfer to the fetus but that will need to be worked out, and assure the safety of doing this treatment obviously.

The other area that we’ll need to look at before we come closer to treating in humans is whether or not this is just correcting the growth disturbance, or there are other problems with intrauterine growth restriction. Those babies are at increased risk of obesity, cardiovascular complications, diabetes, and impaired cognitive development. So one of the questions is, ‘are we making bigger animals, or are we making bigger animals and reprogramming the fetus in all these different ways as well?’ So, we are actually doing ongoing studies, which will be very exciting to see if it corrects not only the growth restriction, but also the predisposition to adult disease, which is a huge problem in our society.

So, we have some ways to go and we certainly need to look mechanistically. Are we making bigger babies but not treating the hypoxia that goes along with these small babies as well? We have a lot of different areas that we are looking into before we move on. Hopefully in the future, years down the line, this will be an innovative, new strategy to look at treatment for a disease for which we have no treatment right now, short of timely delivery.

The other interesting and very exciting area is the whole concept of placental gene therapy, and really this was a proof of concept study. But there are many other obstetrical diseases, again, for which we have very little in the way of treatment options: preterm labor, preeclampsia, brain injury associated with in utero inflammation that may be amenable to this type of treatment with placental gene therapy.

Alix Boyle: Sounds really exciting. Thanks very much Dr. Harkness.