Major league baseball star and his wife turn to IVF to conceive child free of Huntington’s Disease

Joe Smith, pitcher for the Houston Astros, and his wife, sports reporter Allie LaForce. Smith’s family carries the gene for Huntington’s Disease. Photo courtesy of Huntington’s Disease Society for America website.

For many couples, one of the most monumental moments in life is the decision made to conceive a child together and start a family. The usual questions that come to mind typically relate to simple matters such as potential baby names, diapers, clothes, pacifiers, cribs, blankets, and stuffed animals. New parents will also think about what customs, languages, and set of principles they want to pass along to their child. But what if there was something they didn’t want to pass along to their child? What if there was a 50/50 chance of unintentionally passing along a debilitating genetic condition? For Houston Astros pitcher Joe Smith and his wife, sports reporter Allie LaForce, this situation was a devastating reality.

Joe’s grandmother and mother were both diagnosed with Huntington’s Disease (HD), so he has seen first hand the debilitating effects of this condition. HD is a genetically inherited, neurological condition that causes the progressive breakdown of nerve cells in the brain and has no known cure. It gradually deteriorates a person’s mental and physical abilities, making it difficult to recall things, walk, or even speak. According to statistics from Huntington’s Disease Society for America (HDSA), every child of a parent with HD has a 50/50 chance of inheriting the disease. Furthermore, there are approximately 30,000 Americans living with HD and 200,000 at-risk of inheriting the condition. It is because of these high risks that Joe and Allie have decided to conceive a child with the aid of in-vitro fertilization (IVF).

Through IVF, an ovum and sperm are combined outside the body to create a fertilized egg. This egg can be implanted into a woman’s uterus, allowing it to grow and develop. However, there is additional technology known as preimplantation genetic diagnosis (PGD) that can be used alongside IVF. With PGD-IVF, the fertilized eggs can be genetically tested before implantation. In Joe and Allie’s instance, PGD-IVF can be used to screen for HD, ensuring that the fertilized egg does not carry the disease prior to implantation.

In an interview with Morgan Radford on The Today Show, Joe and Allie discuss in detail how HD has impacted their loved ones and their decision to use PGD-IVF. The interview is available here.

In the interview, Joe Smith is quoted as saying, “I’m just taking out a 50/50 chance…I just want that [HD] gone.”

The California Institute for Regenerative Medicine (CIRM) has recently approved a $6 million grant geared towards HD. This funding is for late stage testing needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people. You can read more details about this award from a previous blog post here.

Embryos with abnormal chromosomes can repair themselves

CVS

In a chorionic villus sampling (CVS) test, cells from the fetal side of the placenta are collected and tests for genetic defects.
Image credit: ADAM Health Solutions

Like an increasing number of women, Magdalena Zernicka-Goetz waited later in life to have kids and was pregnant at 44 with her second child. Because older moms have an increased risk of giving birth to children with genetic disorders, Zernicka-Goetz opted to have an early genetic screening test about 12 weeks into her pregnancy. The test, which looks for irregular amounts of chromosomes in the cells taken from the placenta, showed that a quarter of the cells in the developing fetus had genetic abnormalities.

Expectant mothers and tough choices

If she carried the child to term, would the baby have a birth defect? Zernicka-Goetz learned from geneticists that this question was difficult to answer due to a lack of data about what happens to abnormal cells in the developing fetus. Fortunately, her baby was born happy and healthy. But the experience motivated her to seek out a better understanding for the sake of other women who would be faced with similar difficult decisions based on screening tests.

As a professor of developmental biology at Cambridge University, Zernicka-Geotz had the expertise to follow through on this challenge. And in a Nature Communications journal article published yesterday, she and her team report a fascinating result: the very early embryo has the ability to essentially repair itself by getting rid of abnormal cells.

Aneuploidy: You Have the Wrong Number

aneuploidy

Aneuploidy in the developing fetus can lead to genetic disorders. Image credit: Deluca Lab Colorado State University

To reach this finding, the team first had to recreate chromosomal abnormalities in mouse embryos. If you remember your high school or college biology, you’ll recall that before a cell divides, it duplicates each chromosome and then each resulting “daughter” cell grabs one chromosome copy using a retracting spindle fiber structure. The scientists took advantage of the fact that treating dividing cells with the drug reversine destabilizes the spindle fibers and in turn causes an unequal divvying up of the chromosomes between the daughter cells. In scientific jargon the condition is called aneuploidy.

Rescuing the embryo by cellular suicide

Blog embryo repair fig 3

Generating early mouse embryos with an equal mix of normal cells and cells with abnormal chromosome numbers (induced via reversine treatment). Image credit: Bolton et al. Nat Commun. 2016 Mar 29;7:11165

The researchers created mosaic embryos at the eight cell stage in which half the cells had a normal set of chromosomes while the other half we’re the reversine-treated cells with abnormal numbers of chromosomes. With these genetically mosaic embryos, the team tagged the cells with fluorescent dye and used time-lapsed imaging to track the fate of each cell for 48 hours. They found a decrease specifically in the portion of cells that stemmed from the abnormal cells.

A follow up experiment examined cell death as a way to help explain the reduced number of abnormal cells. The researchers found that compared to the normal set of cells in the embryo, the abnormal cells had a significantly higher evidence of apoptosis, or programmed cell death, a natural process that occurs to eliminate harmful or damaged cells. According to Zernicka-Geota and the team, this is the first study to directly show the elimination of abnormal cells in the growing embryo.

Screen Shot 2016-03-30 at 11.25.43 AM.png

Time lapse images showing an abnormal cell (green cell indicated by arrow) being eliminated by apoptosis (programmed cell death) and then engulfed by normal (red) cells (engulfment indicated by star).
Image credit: Bolton et al. Nat Commun. 2016 Mar 29;7:11165

To look at their fate beyond the very early stages of development, the mosaic mouse embryos were implanted into foster mothers and allowed to develop to full term. Thirteen of the twenty-six embryos transferred to foster mothers gave rise to live pups which were all healthy after four months of age.

As Zermicka-Geota stated in a university press release picked up by Medical Express, if these findings reflect what goes on in human development, then decisions based on genetic screening results may not be clear cut:

“We found that even when half of the cells in the early stage embryo are abnormal, the embryo can fully repair itself. It will mean that even when early indications suggest a child might have a birth defect because there are some, but importantly not all abnormal cells in its embryonic body, this isn’t necessarily the case.”

Implications for genetic testing on days-old IVF embryos

These new results don’t suggest that current genetic testing is obsolete. For instance, the amniocentesis test, which collects fetal tissue from the mother’s amniotic fluid between 14 and 20 weeks of pregnancy, can detect genetic disorders with 98-99% accuracy. But this study may have important implications for testing done much earlier. When couples conceive via in vitro fertilization, a so-called pre-implantation genetic diagnosis (PGD) test can be performed on embryos that are only a few days old. In the test, a single cell is removed – without damaging the embryo – and the cell is tested for chromosomal defects. Based on this study, a positive PGD test may be misleading if that abnormal cell was destined to be eliminated from the embryo.

Stem Cell Stories that Caught our Eye: Parkinson’s, Multiple Sclerosis and the Art of Science

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

The technique for removing the nucleus from an egg [Courtesy Oregon Health Sciences University ]

The technique for removing the nucleus from an egg [Courtesy Oregon Health Sciences University ]

Three parent embryos called safe. A scientific review panel in the United Kingdom has issued a report saying that a controversial fertility treatment that uses three parents is likely to be safe. The in vitro fertilization technique is being developed to help women who carry rare genetic mutations have healthy children. While we inherit most of our DNA from the chromosomes in the nucleus of mom’s egg and dad’s sperm, a small organelle outside the nucleus, called the mitochondria, also carries a few genes. Those we inherit only from mom, since her egg hosts those at the point of fertilization. This technique puts mom’s nucleus into the egg of a healthy donor that has had its nucleus removed but still has the healthy mitochondria. Gretchen Vogel, who worked with me as an intern several years ago, did a nice job explaining the process in Science Insider.

Embryonic cells show promise in multiple sclerosis. The vast majority of stem cell clinical trials registered at clinicaltrials.gov use a type of stem cell found in bone marrow, fat and cord blood called mesenchymal stem cells (MSCs). But many in the field believe that sometimes those cells are a little too mature to get the job done well. They suggest that in some situations these cells are often only minimally effective at the goals for their use: reducing inflammation and secreting factors that stimulate natural healing. So several groups have started maturing embryonic stem cells into early stage MSCs hoping their youth would make them more robust in these functions. Now, a team from the company ImStem Biotechnology and the University of Connecticut has shown that this is indeed the case—at least in the model in this study. They published in Stem Cell Reports that embryonic-derived MSCs were better at reducing the damage of multiple sclerosis in mice. The company’s press release was picked up at SFGate.

You can read about CIRM-funded work in the field on our multiple sclerosis fact sheet.

Transplanted cells survive 14 years in Parkinson’s. A Parkinson’s pioneer I wrote about often at Harvard has published important data showing transplanted nerves can survive and continue producing the dopamine needed in Parkinson’s for many years. Ole Isacson, of Harvard-affiliate McLean Hospital, reported that five patients who had nerves transplanted as much as 14 years before, all showed evidence that those nerves where still functioning at the time of their death. Those deaths, by the way, were unrelated to their Parkinson’s. As many teams are preparing to transplant nerve cells from much more readily available stem cells, the fact that these cells can persist is definitely good news. HEALTHCANAL ran the institution’s press release.

CIRM gathered most of the world leaders in the field last year to discuss next steps and we produced this white paper “Cell Therapies for Parkinson’s Disease from Discovery to Clinic.”

Adult stem cells alert to damage. I often find myself explaining adult stem cells to patients and family members calling CIRM seeking some clarity for an admittedly confusing field. In explaining that we have tissue-specific stem cells in most parts of our bodies all the time, I end up talking about those cells waiting around for a signal to respond to damage or inflammation. A longevity researcher at Stanford, Thomas Rando, has given a name to this in a new paper published in Natiure last week. He calls it the “alert” state. Krista Conger provides a good explanation of his findings in the school of medicine’s blog Scope.

Science as art takes to the runways. I have always had a bit of a bully pulpit about wanting to tear down the wall between C.P. Snow’s two cultures: science and humanities. So, I love the fact that more and more groups are seeing that contemporary imaging technologies in the lab often naturally bridge the gap between art and science. Two of the nation’s airports this week opened new exhibits featuring the art of science. Dulles airport outside of our nation’s capital teamed up with the National Institutes of Health for an exhibit described in the NIH blog. And the Southern California biotech trade association BioCom created a display in the San Diego airport timed to the BIO International Convention scheduled to convene there June 24. This display incudes an image from CIRM that a Salk Institute researcher had submitted to the imaging contest we ran my first year here in 2008. All those contest images are available free for educational uses at our Flickr site.

Stem Cell Stories that Caught our Eye: Parkinson’s, Multiple Sclerosis and the Art of Science

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

The technique for removing the nucleus from an egg [Courtesy Oregon Health Sciences University ]

The technique for removing the nucleus from an egg [Courtesy Oregon Health Sciences University ]

Three parent embryos called safe. A scientific review panel in the United Kingdom has issued a report saying that a controversial fertility treatment that uses three parents is likely to be safe. The in vitro fertilization technique is being developed to help women who carry rare genetic mutations have healthy children. While we inherit most of our DNA from the chromosomes in the nucleus of mom’s egg and dad’s sperm, a small organelle outside the nucleus, called the mitochondria, also carries a few genes. Those we inherit only from mom, since her egg hosts those at the point of fertilization. This technique puts mom’s nucleus into the egg of a healthy donor that has had its nucleus removed but still has the healthy mitochondria. Gretchen Vogel, who worked with me as an intern several years ago, did a nice job explaining the process in Science Insider.

Embryonic cells show promise in multiple sclerosis. The vast majority of stem cell clinical trials registered at clinicaltrials.gov use a type of stem cell found in bone marrow, fat and cord blood called mesenchymal stem cells (MSCs). But many in the field believe that sometimes those cells are a little too mature to get the job done well. They suggest that in some situations these cells are often only minimally effective at the goals for their use: reducing inflammation and secreting factors that stimulate natural healing. So several groups have started maturing embryonic stem cells into early stage MSCs hoping their youth would make them more robust in these functions. Now, a team from the company ImStem Biotechnology and the University of Connecticut has shown that this is indeed the case—at least in the model in this study. They published in Stem Cell Reports that embryonic-derived MSCs were better at reducing the damage of multiple sclerosis in mice. The company’s press release was picked up at SFGate.

You can read about CIRM-funded work in the field on our multiple sclerosis fact sheet.

Transplanted cells survive 14 years in Parkinson’s. A Parkinson’s pioneer I wrote about often at Harvard has published important data showing transplanted nerves can survive and continue producing the dopamine needed in Parkinson’s for many years. Ole Isacson, of Harvard-affiliate McLean Hospital, reported that five patients who had nerves transplanted as much as 14 years before, all showed evidence that those nerves where still functioning at the time of their death. Those deaths, by the way, were unrelated to their Parkinson’s. As many teams are preparing to transplant nerve cells from much more readily available stem cells, the fact that these cells can persist is definitely good news. HEALTHCANAL ran the institution’s press release.

CIRM gathered most of the world leaders in the field last year to discuss next steps and we produced this white paper “Cell Therapies for Parkinson’s Disease from Discovery to Clinic.”

Adult stem cells alert to damage. I often find myself explaining adult stem cells to patients and family members calling CIRM seeking some clarity for an admittedly confusing field. In explaining that we have tissue-specific stem cells in most parts of our bodies all the time, I end up talking about those cells waiting around for a signal to respond to damage or inflammation. A longevity researcher at Stanford, Thomas Rando, has given a name to this in a new paper published in Natiure last week. He calls it the “alert” state. Krista Conger provides a good explanation of his findings in the school of medicine’s blog Scope.

Science as art takes to the runways. I have always had a bit of a bully pulpit about wanting to tear down the wall between C.P. Snow’s two cultures: science and humanities. So, I love the fact that more and more groups are seeing that contemporary imaging technologies in the lab often naturally bridge the gap between art and science. Two of the nation’s airports this week opened new exhibits featuring the art of science. Dulles airport outside of our nation’s capital teamed up with the National Institutes of Health for an exhibit described in the NIH blog. And the Southern California biotech trade association BioCom created a display in the San Diego airport timed to the BIO International Convention scheduled to convene there June 24. This display incudes an image from CIRM that a Salk Institute researcher had submitted to the imaging contest we ran my first year here in 2008. All those contest images are available free for educational uses at our Flickr site.