CIRM-Funded Clinical Trials Targeting Blood and Immune Disorders

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Today we are featuring trials in our blood and immune disorders portfolio, specifically focusing on sickle cell disease, HIV/AIDS, severe combined immunodeficiency (SCID, also known as bubble baby disease) and rare disease called chronic granulomatous disease (CGD).

CIRM has funded a total of eight trials targeting these disease areas, all of which are currently active. Check out the infographic below for a list of those trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

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From trauma to treatment: a Patient Advocate’s journey from helping her son battle a deadly disease to helping others do the same

Everett SCID 1

For every clinical trial CIRM funds we create a Clinical Advisory Panel or CAP. The purpose of the CAP is to make recommendations and provide guidance and advice to both CIRM and the Project Team running the trial. It’s part of our commitment to doing everything we can to help make the trial a success and get therapies to the people who need them most, the patients.

Each CAP consists of three to five members, including a Patient Advocate, an external scientific expert, and a CIRM Science Officer.

Having a Patient Advocate on a CAP fills a critical need for insight from the patient’s perspective, helping shape the trial, making sure that it is being carried out in a way that has the patient at the center. A trial designed around the patient, and with the needs of the patient in mind, is much more likely to be successful in recruiting and retaining the patients it needs to see if the therapy works.

One of the clinical trials we are currently funding is focused on severe combined immunodeficiency disease, or SCID. It’s also known as “bubble baby” disease because children with SCID are born without a functioning immune system, so even a simple virus or infection can prove fatal. In the past some of these children were kept inside sterile plastic bubbles to protect them, hence the name “bubble baby.”

Everett SCID family

Anne Klein is the Patient Advocate on the CAP for the CIRM-funded SCID trial at UCSF and St. Jude Children’s Research Hospital. Her son Everett was born with SCID and participated in this clinical trial. We asked Anne to talk about her experience as the mother of a child with SCID, and being part of the research that could help cure children like Everett.

“When Everett was born his disease was detected through a newborn screening test. We found out he had SCID on a Wednesday, and by  Thursday we were at UCSF (University of California, San Francisco). It was very sudden and quite traumatic for the family, especially Alden (her older son). I was abruptly taken from Alden, who was just two and a half years old at the time, for two months. My husband, Brian Schmitt, had to immediately drop many responsibilities required to effectively run his small business. We weren’t prepared. It was really hard.”

(Everett had his first blood stem cell transplant when he was 7 weeks old – his mother Anne was the donor. It helped partially restore his immune system but it also resulted in some rare, severe complications as a result of his mother’s donor cells attacking his body. So when, three years later, the opportunity to get a stem cell therapy came along Anne and her husband, Brian, decided to say yes. After some initial problems following the transplant, Everett seems to be doing well and his immune system is the strongest it has ever been.)

“It’s been four years, a lot of ups and downs and a lot of trauma. But it feels like we have turned a corner. Everett can go outside now and play, and we’re hanging out more socially because we no longer have to be so concerned about him being exposed to germs or viruses.

His doctor has approved him to go to daycare, which is amazing. So, Everett is emerging into the “normal” world for the first time. It’s nerve wracking for us, but it’s also a relief.”

Everett SCID in hospital

How Anne came to be on the CAP

“Dr. Cowan from UCSF and Dr. Malech from the NIH (National Institutes of Health) reached out to me and asked me about it a few months ago. I immediately wanted to be part of the group because, obviously, it is something I am passionate about. Knowing families with SCID and what they go through, and what we went through, I will do everything I can to help make this treatment more available to as many people as need it.

I can provide insight on what it’s like to have SCID, from the patient perspective; the traumas you go through. I can help the doctors and researchers understand how the medical community can be perceived by SCID families, how appreciative we are of the medical staff and the amazing things they do for us.

I am connected to other families, both within and outside of the US, affected by this disease so I can help get the word out about this treatment and answer questions for families who want to know. It’s incredibly therapeutic to be part of this wider community, to be able to help others who have been diagnosed more recently.”

The CAP Team

“They were incredibly nice and when I did speak they were very supportive and seemed genuinely interested in getting feedback from me. I felt very comfortable. I felt they were appreciative of the patient perspective.

I think when you are a research scientist in the lab, it’s easy to miss the perspective of someone who is actually experiencing the disease you are trying to fix.

At the NIH, where Everett had his therapy, the stem cell lab people work so hard to process the gene corrected cells and get them to the patient in time. I looked through the window into the hall when Everett was getting his therapy and the lab staff were outside, in their lab coats, watching him getting his new cells infused. They wanted to see the recipient of the life-saving treatment that they prepared.

It is amazing to see the process that the doctors go through to get treatments approved. I like being on the CAP and learning about the science behind it and I think if this is successful in treating others, then that would be the best reward.”

The future:

“We still have to fly back to the NIH, in Bethesda, MD, every three months for checkups. We’ll be doing this for 15 years, until Everett is 18. It will be less frequent as Everett gets older but this kind of treatment is so new that it’s still important to do this kind of follow-up. In between those trips we go to UCSF every month, and Kaiser every 1-3 weeks, sometimes more.

I think the idea of being “cured”, when you have been through this, is a difficult thing to think about. It’s not a word I use lightly as it’s a very weighted term. We have been given the “all clear” before, only to be dealt setbacks later. Once he’s in school and has successfully conquered some normal childhood illnesses, both Brian and I will be able to relax more.

One of Everett’s many doctors once shared with me that, in the past, he sometimes had to tell parents of very sick children with SCID that there was nothing else they could do to help them. So now to have a potential treatment like this, he was so excited about a stem cell therapy showing such promise.

One thing we think about Everett and Alden, is that they are both so young and have been through so much already. I’m hoping that they can forget all this and have a chance to grow up and lead a normal life.”

Stem Cell Stories that Caught our Eye: stem cell insights into anorexia, Zika infection and bubble baby disease

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.

Stem cell model identifies new culprit for anorexia.

Eating disorders like anorexia nervosa are often thought to be caused by psychological disturbances or societal pressure. However, research into the genes of anorexia patients suggests that what’s written in your DNA can be associated with an increased vulnerability to having this disorder. But identifying individual genes at fault for a disease this complex has remained mostly out of scientists’ reach, until now.

A CIRM-funded team from the UC San Diego (UCSD) School of Medicine reported this week that they’ve developed a stem cell-based model of anorexia and used it to identify a gene called TACR1, which they believe is associated with an increased likelihood of getting anorexia.

They took skin samples from female patients with anorexia and reprogrammed them into induced pluripotent stem cells (iPSCs). These stem cells contained the genetic information potentially responsible for causing their anorexia. The team matured these iPSCs into brain cells, called neurons, in a dish, and then studied what genes got activated. When they looked at the genes activated by anorexia neurons, they found that TACR1, a gene associated with psychiatric disorders, was switched on higher in anorexia neurons than in healthy neurons. These findings suggest that the TACR1 gene could be an identifier for this disease and a potential target for developing new treatments.

In a UCSD press release, Professor and author on the study, Alysson Muotri, said that they will follow up on their findings by studying stem cell lines derived from a larger group of patients.

Alysson Muotri UC San Diego

“But more to the point, this work helps make that possible. It’s a novel technological advance in the field of eating disorders, which impacts millions of people. These findings transform our ability to study how genetic variations alter brain molecular pathways and cellular networks to change risk of anorexia nervosa — and perhaps our ability to create new therapies.”

Anorexia is a disease that affects 1% of the global population and although therapy can be an effective treatment for some, many do not make a full recovery. Stem cell-based models could prove to be a new method for unlocking new clues into what causes anorexia and what can cure it.

Nature versus Zika, who will win?

Zika virus is no longer dominating the news headlines these days compared to 2015 when large outbreaks of the virus in the Southern hemisphere came to a head. However, the threat of Zika-induced birth defects, like microcephaly to pregnant women and their unborn children is no less real or serious two years later. There are still no effective vaccines or antiviral drugs that prevent Zika infection but scientists are working fast to meet this unmet need.

Speaking of which, scientists at UCLA think they might have a new weapon in the war against Zika. Back in 2013, they reported that a natural compound in the body called 25HC was effective at attacking viruses and prevented human cells from being infected by viruses like HIV, Ebola and Hepatitis C.

When the Zika outbreak hit, they thought that this compound could potentially be effective at preventing Zika infection as well. In their new study published in the journal Immunity, they tested a synthetic version of 25HC in animal and primate models, they found that it protected against infection. They also tested the compound on human brain organoids, or mini brains in a dish made from pluripotent stem cells. Brain organoids are typically susceptible to Zika infection, which causes substantial cell damage, but this was prevented by treatment with 25HC.

Left to right: (1) Zika virus (green) infects and destroys the formation of neurons (pink) in human stem cell-derived brain organoids.  (2) 25HC blocks Zika infection and preserves neuron formation in the organoids. (3) Reduced brain size and structure in a Zika-infected mouse brain. (4) 25HC preserves mouse brain size and structure. Image courtesy of UCLA Stem Cell.

A UCLA news release summarized the impact that this research could have on the prevention of Zika infection,

“The new research highlights the potential use of 25HC to combat Zika virus infection and prevent its devastating outcomes, such as microcephaly. The research team will further study whether 25HC can be modified to be even more effective against Zika and other mosquito-borne viruses.”

Harnessing a naturally made weapon already found in the human body to fight Zika could be an alternative strategy to preventing Zika infection.

Gene therapy in stem cells gives hope to bubble-babies.

Last week, an inspiring and touching story was reported by Erin Allday in the San Francisco Chronicle. She featured Ja’Ceon Golden, a young baby not even 6 months old, who was born into a life of isolation because he lacked a properly functioning immune system. Ja’Ceon had a rare disease called severe combined immunodeficiency (SCID), also known as bubble-baby disease.

 

Ja’Ceon Golden is treated by patient care assistant Grace Deng (center) and pediatric oncology nurse Kat Wienskowski. Photo: Santiago Mejia, The Chronicle.

Babies with SCID lack the body’s immune defenses against infectious diseases and are forced to live in a sterile environment. Without early treatment, SCID babies often die within one year due to recurring infections. Bone marrow transplantation is the most common treatment for SCID, but it’s only effective if the patient has a donor that is a perfect genetic match, which is only possible for about one out of five babies with this disease.

Advances in gene therapy are giving SCID babies like Ja’Ceon hope for safer, more effective cures. The SF Chronicle piece highlights two CIRM-funded clinical trials for SCID run by UCLA in collaboration with UCSF and St. Jude Children’s Research Hospital. In these trials, scientists isolate the bone marrow stem cells from SCID babies, correct the genetic mutation causing SCID in their stem cells, and then transplant them back into the patient to give them a healthy new immune system.

The initial results from these clinical trials are promising and support other findings that gene therapy could be an effective treatment for certain genetic diseases. CIRM’s Senior Science Officer, Sohel Talib, was quoted in the Chronicle piece saying,

“Gene therapy has been shown to work, the efficacy has been shown. And it’s safe. The confidence has come. Now we have to follow it up.”

Ja’Ceon was the first baby treated at the UCSF Benioff Children’s Hospital and so far, he is responding well to the treatment. His great aunt Dannie Hawkins said that it was initially hard for her to enroll Ja’Ceon in this trial because she was a partial genetic match and had the option of donating her own bone-marrow to help save his life. In the end, she decided that his involvement in the trial would “open the door for other kids” to receive this treatment if it worked.

Ja’Ceon Golden plays with patient care assistant Grace Deng in a sterile play area at UCSF Benioff Children’s Hospital.Photo: Santiago Mejia, The Chronicle

It’s brave patients and family members like Ja’Ceon and Dannie that make it possible for research to advance from clinical trials into effective treatments for future patients. We at CIRM are eternally grateful for their strength and the sacrifices they make to participate in these trials.