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.

Breakthrough for type 1 diabetes: scientist discovers how to grow insulin-producing cells

Matthias Hebrok, PhD, senior author of new study that transformed human stem cells into mature, insulin-producing cells. Photo courtesy of UCSF.

More often than not, people don’t really think about their blood sugar levels before sitting down to enjoy a delicious meal, partake in a tasty dessert, or go out for a bicycle ride. But for type 1 diabetes (T1D) patients, every minute and every action revolves around the readout from a glucose meter, a device used to measure blood sugar levels.

Normally, the pancreas contains beta cells that produce insulin in order to maintain blood sugar levels in the normal range. Unfortunately, those with T1D have an immune system that destroys their own beta cells, thereby decreasing or preventing the production of insulin and in turn the regulation of blood sugar levels. Chronic spikes in blood sugar levels can lead to blindness, nerve damage, kidney failure, heart disease, stroke, and even death.

Those with T1D manage their condition by injecting themselves with insulin anywhere from two to four times a day. A light workout, slight change in diet, or even an exciting event can have a serious impact that requires a glucose meter check and an insulin injection.

There are clinical trials involving transplants of pancreatic “islets”, clusters of cells containing healthy beta cells, but these rely on pancreases from deceased donors and taking immune suppressing drugs for life.

But what if there was a way to produce healthy beta cells in a lab without the need of a transplant?

Dr. Matthias Hebrok, director of the UCSF diabetes center, and Dr. Gopika Nair, postdoctoral fellow, have discovered how to transform human stem cells into healthy, insulin producing beta cells.

In a news release written by Dr. Nicholas Weiler of UCSF, Dr. Hebrok is quoted as saying “We can now generate insulin-producing cells that look and act a lot like the pancreatic beta cells you and I have in our bodies. This is a critical step towards our goal of creating cells that could be transplanted into patients with diabetes.”

For the longest time, scientists could only produce cells at an immature stage that were unable to respond to blood sugar levels and secrete insulin properly. Dr. Hebrok and Dr. Nair discovered that mimicking the “islet” formation of cells in the pancreas helped the cells mature. These cells were then transplanted into mice and found that they were fully functional, producing insulin and responding to changes blood sugar levels.

Dr. Hebrok’s team is already in collaboration with various colleagues to make these cells transplantable into patients.

Gopika Nair, PhD, postdoctoral fellow that led the study for transforming human stem cells into mature, insulin-producing cells. Photo courtesy of UCSF.

Dr. Nair in the article is also quoted as saying “Current therapeutics like insulin injections only treat the symptoms of the disease. Our work points to several exciting avenues to finally finding a cure.”

“We’re finally able to move forward on a number of different fronts that were previously closed to us,” Hebrok added. “The possibilities seem endless.” 

Dr. Hebrok, who is also a member of the CIRM funded UCSF Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, was senior author of the new study, which was published February 1, 2019 in Nature Cell Biology.

CIRM has funded three separate human clinical trials for T1D that total approximately $37.8 million in awards. Two of these trials are being conducted by ViaCyte, Inc. and the third trial is being conducted by Caladrius Biosciences.

Gene therapy and blood stem cells cure sickle cell disease patients

Sickle-shaped blood cells. The cells become lodged in blood vessels, causing strokes or excruciating pain as blood stops flowing. Photo courtesy of Omikron/Science Source

Blood is the lifeline of the body. The continuous, unimpeded circulation of blood maintains oxygen flow throughout the body and enables us to carry out our everyday activities. Unfortunately, there are individuals whose own bodies are in a constant battle that prevents this from occurring seamlessly. They have something known as sickle cell disease (SCD), an inherited condition caused by a mutation in a single gene. Rather than producing normal, circular red blood cells, their bodies produce sickle shaped cells (hence the name) that can become lodged in blood vessels, preventing blood flow. The lack of blood flow can cause agonizing pain, known as crises, as well as strokes. Chronic crises can cause organ damage, which can eventually lead to organ failure. Additionally, since the misshapen cells don’t survive long in the body, people with SCD have a greater risk of being severely anemic and are more prone to infections. Monthly blood transfusions are often needed to help temporarily alleviate symptoms. Due to the debilitating nature of SCD, important aspects of everyday life such as employment and health insurance can be extremely challenging to find and maintain.

An estimated 100,000 people in the United States are living with SCD. Around the world, about 300,000 infants are born with the condition each year, a statistic that will increase to 400,000 by 2050 according to one study. Many people with SCD do not live past the age of 50. It is most prevalent in individuals with sub-Saharan African descent followed by people of Hispanic descent. Experts have stated that advances in treatment have been limited in part because SCD is concentrated in poorer minority communities.

Despite these grim statistics and prognosis, there is hope.

The New York Times and Boston Herald recently released featured articles that tell the personal stories of patients enrolled in a clinical trial conducted by bluebird bio. The trial uses gene therapy in combination with hematopoietic (blood) stem cells (HSCs) to give rise to normal red blood cells in SCD patients.

Here are the stories of these patients. To read the full New York Times article, click here. For the Boston Herald article, click here.

Brothers, Emmanuel “Manny” 21 and Aiden Johnson 7 at their home in Brockton, Massachusetts. Both brothers were born with sickle cell disease. Photo courtesy of Matt Stone for MediaNews Group/Boston Herald

Emmanuel “Manny” Johnson was the very first patient in the SCD trial. He was motivated to participate in the trial not just for himself but for his younger brother Aiden Johnson, who was also born with SCD. Manny has a tattoo with Aiden’s name written inside a red sickle cell awareness ribbon.

In the article Manny is quoted as saying “It’s not only that we share the same blood disease, it’s like I have to do better for him.”

Since receiving the treatment, Manny’s SCD symptoms have disappeared.

Brandon Williams received the stem cell gene therapy to replace sickle cells with healthy red blood cells. The tattoo on his right forearm is in honor of his sister, Britney, who died of sickle cell disease. Photo courtesy of Alyssa Schukar for The New York Times

For Brandon Williams of Chicago, the story of SCD is a very personal one. At just 21 years old, Brandon had suffered four strokes by the time he turned 18. His older sister, Britney Williams, died of sickle cell disease at the age of 22. Brandon was devastated and felt that his own life could end at any moment. He was then told about the SCD trial and decided to enroll. Following the treatment, his symptoms have vanished along with the pain and fear inflicted by the disease.

Carmen Duncan participated in the stem cell gene therapy trial and no longer has sickle-cell symptoms. She wants to join the military, something that wasn’t an option until now. Photo courtesy of Sean Rayford for The New York Times

The NY Times piece also profiles Carmen Duncan, a 20 year old from Charleston, South Carolina. She had her spleen removed when she was just two years old as a result of complications form SCD. Duncan spent a large portion of her childhood in hospitals, coping with the pain in her arms and legs from blocked blood vessels. She enrolled in the SCD trial as well and she no longer has any signs of SCD. Duncan had aspirations to join the military but was unable to because of her condition. Now that she is symptom free, she plans to enlist.

This SCD clinical trial has multiple trial sites across the US, one which is the UCSF Alpha Stem Cell Clinic , a CIRM funded clinic specializing in the delivery of stem cell clinical trials to patients. CIRM awarded a $7,999,999 grant to help establish this site.

Targeted treatment for pediatric brain tumors shows promising results

Image of medulloblastoma

Imagine sitting in the doctor’s office and being told the heartbreaking news that your child has been diagnosed with a malignant brain tumor. As one might expect, the doctor states that the most effective treatment option is typically a combination of chemotherapy and radiation. However, the doctor reveals that there are additional risks to take into account that apply to children. Since children’s tiny bodies are still growing and developing, chemotherapy and radiation can cause long-term side effects such as intellectual disabilities. As a parent, it is painful enough to have to watch a child go through chemotherapy and radiation without adding permanent damage into the fold.

Sadly, this scenario is not unique. Medulloblastoma is the most prevalent form of a pediatric brain tumor with more than 350 children diagnosed with cancer each year. There are four distinct subtypes of medulloblastoma, with the deadliest being known as Group 3.

Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) are trying to minimize the collateral damage by finding personalized treatments that reduce side effects while remaining effective. Scientists at SBP are working with an inhibitor known as LSD1 that specifically targets Group 3 medulloblastoma in a mouse model. The study, published in Nature Communications, showed that the drug dramatically decreased the size of tumors grown under the mouse’s skin by shrinking the cancer by more than 80 percent. This suggested that it could also be effective against patients’ tumors if it could be delivered to the brain. The LSD1 inhibitor has shown promise in clinical trials, where it has been tested for treating other types of cancer.

According to Robert Wechsler-Reya, Ph.D., senior author of the paper and director of the Tumor Initiation and Maintenance Program at SBP: “Our lab is working to understand the genetic pathways that drive medulloblastoma so we can find better ways to intervene and treat tumors. This study shows that a personalized treatment based upon a patient’s specific tumor type might be within our reach.”

Dr. Wechsler-Reya’s work on medulloblastoma was, in part, funded by the CIRM (LA1-01747) in the form of a Research Leadership Award for $5,226,049.