Battling COVID and turning back the clock on stem cell funding

Coronavirus

Battling the virus that causes COVID-19 is something that is top of everyone’s mind right now. That’s why CIRM is funding 17 different projects targeting the virus. But one of the most valuable tools in helping develop vaccines against a wide variety of diseases in the past is now coming under threat. We’ll talk about both issues in a live broadcast we’re holding on Wednesday, October 14th at noon (PDT).

That date is significant because it’s Stem Cell Awareness Day and we thought it appropriate to host a meeting looking at two of the most important issues facing the field.

The first part of the event will focus on the 17 projects that CIRM is funding that target COVID-19. This includes three clinical trials aiming to treat people who have been infected with the virus and are experiencing some of the more severe effects, such as damaged lungs.

We’ll also look at some of the earlier stage research that includes:

  • Work to help develop a vaccine
  • Using muscle stem cells to help repair damage to the diaphragm in patients who have spent an extended period on a ventilator
  • Boosting immune system cells to help fight the virus

The second part of the event will look at ways that funding for stem cell research at the federal level is once again coming into question. The federal government has already imposed new restrictions on funding for fetal tissue research, and now there are efforts in Congress to restrict funding for embryonic stem cell research.

The impacts could be significant. Fetal tissue has been used for decades to help develop some of the most important vaccines used today including rubella, chickenpox, hepatitis A, and shingles. They have also been used to make approved drugs against diseases including hemophilia, rheumatoid arthritis, and cystic fibrosis.

We’ll look at some of the reasons why we are seeing these potential restrictions on the medical research and what impact they could have on the ability to develop new treatments for the coronavirus and other deadly diseases.

You can watch the CIRM Stem Cell Awareness Day live event by going here: https://www.youtube.com/c/CIRMTV/videos at noon on Wednesday, October 14th.

Feel free to share news about this event with anyone you think might be interested.

We look forward to seeing you there.

CIRM funded study results in the first ever in utero stem cell transplant to treat alpha thalassemia

Mackenzie

Dr. Tippi MacKenzie (left) of UCSF Benioff Children’s Hospital San Francisco, visits with newborn Elianna and parents Nichelle Obar and Chris Constantino. Photo by Noah Berger

Imagine being able to cure a genetic disorder before a baby is even born. Thanks to a CIRM funded study, what would have been a mere dream a couple of years ago has become a reality.

Drs. Tippi MacKenzie and Juan Gonzalez Velez of the University of California San Francisco (UCSF) have successfully treated alpha thalassemia in Elianna Constantino, using stem cells from her mother’s bone marrow. Alpha thalassemia is part of a group of blood disorders that impairs the body’s ability to produce hemoglobin, the molecule that is responsible for transporting oxygen throughout the body on red blood cells. Present in approximately 5% of the population, alpha thalassemia is particularly prevalent among individuals of Asian heritage. Treatment options for this disease are severely limited, generally requiring multiple rounds of blood transfusions or a bone marrow transplant which requires immunosuppressive therapy. Normally, fetuses die in the womb or the pregnancy is aborted because of the poor prognosis.

The revolutionary treatment pioneered at UCSF involved isolating blood stem cells (cells that are capable of turning into all blood cell types) from the mother’s bone marrow and injecting these cells into Elianna’s bloodstream via the umbilical vein. The doctors were able to observe the development of healthy blood cells in the baby’s blood stream, allowing for efficient oxygen transport throughout the baby’s body. Because the cells were transplanted at the fetal stage, a time when the immune system is not fully developed, there was low risk of rejection and the transplant occurred without aggressive immunosuppressive therapy.

The baby was born healthy earlier this year and has been allowed to return home. While it is still too early to tell how effective this treatment will be in the long term, it is very encouraging that both the mother and baby have endured the treatment thus far.

In a press release, Dr. MacKenzie states:

“Her healthy birth suggests that fetal therapy is a viable option to offer to families with this diagnosis.”

The in utero stem cell transplant was performed as part of a clinical trial conducted at the UCSF Benioff Children’s Hospitals in San Francisco and Oakland. The trial is currently enrolling 10 pregnant women to test the safety and effectiveness of this treatment over a wider population.

If successful, this type of treatment is particularly exciting because it could be expanded to other types of hereditary blood disorders such as sickle cell anemia and hemophilia.

 

 

 

Coming up with a stem cell FIX for a life-threatening blood disorder

Hemophilia

A promising new treatment option for hemophiliacs is in the works at the Salk Institute for Biological Sciences. Patients with Hemophilia B experience uncontrolled, and sometimes life threatening, bleeding due to loss or improper function of Factor IX (FIX), a protein involved in blood clotting. There is no cure for the disease and patients rely on routine infusions of FIX to prevent excessive blood loss. As you can imagine, this treatment regimen is both time consuming and expensive, while also becoming less effective over time.

Salk researchers, partially funded by CIRM, aimed to develop a more long-term solution for this devastating disease by using the body’s own cells to fix the problem.

In the study, published in the journal Cell Reports, They harvested blood cells from hemophiliacs and turned them into iPSCs (induced pluripotent stem cells), which are able to turn into any cell type. Using gene editing, they repaired the iPSCs so they could produce FIX and then turned the iPSCs into liver cells, the cell type that naturally produces FIX in healthy individuals.

One step therapy

To test whether these FIX-producing liver cells were able to reduce excess blood loss, the scientists injected the repaired human cells into a hemophiliac mouse. The results were very encouraging; they saw a greater than two-fold increase in clotting efficiency in the mice, reaching about a quarter of normal activity. This is particularly promising because other studies showed that increasing FIX activity to this level in hemophiliac humans significantly reduces bleeding rates. On top of that they also observed that these cells were able to survive and produce FIX for up to a year in the mice.

In a news release Suvasini Ramaswamy, the first author of the paper, said this method could eliminate the need for multiple treatments, as well as avoiding the immunosuppressive therapy that would be required for a whole liver transplant.

“The appeal of a cell-based approach is that you minimize the number of treatments that a patient needs. Rather than constant injections, you can do this in one shot.”

While these results provide an exciting new avenue in hemophilia treatment, there is still much more work that needs to be done before this type of treatment can be used in humans. This approach, however, is particularly exciting because it provides an important proof of principle that combining stem cell reprogramming with genetic engineering can lead to life-changing breakthroughs for treating genetic diseases that are not currently curable.