alpha thalassemia

Performance, Passion and Progress: and that’s just page one of our 2018 Annual Report

/ Kevin McCormack / Leave a comment

2018_ar_webimage

It’s hard to sum up the activities and achievements of a year in a single document, let alone one that’s just 24 pages. But that’s what we have done in putting together our 2018 Annual Report.

It’s a look back at the year just gone, the highlights, the low lights (spoiler alert – there weren’t any) and the impact we had on the field of stem cell research. But it’s far more than that. It’s also a look ahead. A look at the challenges we face, and profiles of the people who are going to help us overcome those challenges and maintain our progress.

And people are truly at the heart of this report, from UC San Francisco’s Dr. Tippi MacKenzie who is on the front cover for her work in developing an in-utero treatment for the almost always fatal disorder alpha thalassemia major (and the photo of the baby and mom whose lives were changed by that therapy) to Rich Lajara on the back cover, the first person ever treated in a CIRM-funded clinical trial.

Inside are an array of simple images designed to reflect how we as a state agency have performed this year. The numbers themselves tell a powerful story:

  • 50 clinical trials funded to date, 7 this year alone
  • $2.6 billion in CIRM grants has been leveraged to bring in an additional $3.2 billion in matching funds and investments from other sources.
  • 1,180 patients have been involved in CIRM clinical trials

We know people don’t have a lot of time to read Annual Reports so we have made this as visually engaging and informative as possible. We want you to get a real sense of who we are, what we have done and who has helped us do that without you having to wade through a document the size of War and Peace (great book by the way – the Russians beat Napoleon).

We think we have a great story to tell. This Annual Report is one chapter in that story. We hope you like it.

 

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

/ Pallavi Penumetcha / Leave a comment
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.

 

 

 

Stem cell stories that caught our eye: bubble baby therapy a go in UK, in-utero stem cell trial and novel heart disease target

/ Todd Dubnicoff / Leave a comment

There were lots of CIRM mentions in the news this week. Here are two brief recaps written by Karen Ring to get you up to speed. A third story by Todd Dubnicoff summarizes an promising finding related to heart disease by researchers in Singapore.  

CIRM-funded “bubble baby” disease therapy gets special designation by UK.
Orchard Therapeutics, a company based in the UK and the US, is developing a stem cell-based gene therapy called OTL-101 to treat a primary immune disease called adenosine-deaminase deficient severe combined immunodeficiency (ADA-SCID), also known as “bubble baby disease”. CIRM is funding a Phase 1/2 clinical trial led by Don Kohn of UCLA in collaboration with Orchard and the University College in London.

In July, the US Food and Drug Administration (FDA) awarded OTL-101 Rare Pediatric Disease Designation (read more about it here), which makes the therapy eligible for priority review by the FDA, and could give it a faster route to being made more widely available to children in need.

On Tuesday, Orchard announced further good news that OTL-101 received “Promising Innovative Medicine Designation” by the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA). In a news release, the company explained how this designation bodes well for advancing OTL-101 from clinical trials into patients,

“The designation as Promising Innovative Medicine is the first step of a two-step process under which OTL-101 can benefit from the Early Access to Medicine Scheme (“EAMS”). Nicolas Koebel, Senior Vice President for Business Operations at Orchard, added: “With this PIM designation we can potentially make OTL-101 available to UK patients sooner under the Early Access to Medicine Scheme”.

CIRM funded UCSF clinical trial mentioned in SF Business Times
Ron Leuty, reporter at the San Francisco Business Times, published an article about a CIRM-funded trial out of UCSF that is targeting a rare genetic blood disease called alpha thalassemia major, describing it as, “The world’s first in-utero blood stem cell transplant, soon to be performed at the University of California, San Francisco, could point the way toward pre-birth cures for a range of blood diseases, such as sickle cell disease.”

Alpha Thalassemia affects the ability of red blood cells to carry oxygen because of a reduction in a protein called hemoglobin. The UCSF trial, spearheaded by UCSF Pediatric surgeon Dr. Tippi MacKenzie, is hoping to use stem cells from the mother to treat babies in the womb to give them a better chance at surviving after birth.

In an interview with Leuty, Tippi explained,

“Our goal is to put in enough cells so the baby won’t need another transplant. But even if we fall short, if we can just establish 1 percent maternal cells circulating in the child, it will establish tolerance and then they can get the booster transplant.”

She also emphasized the key role that CIRM funded played in the development and launch of this clinical trial.

“CIRM is about more than funding for studies, MacKenzie said. Agency staff has provided advice about how to translate animal studies into work in humans, she said, as well as hiring an FDA consultant, writing an investigational new drug application and setting up a clinical protocol.”

“I’m a clinician, but running a clinical trial is different,” MacKenzie said. “CIRM’s been incredibly helpful in helping me navigate that.”

Heart, heal thyself: the story of Singheart
When you cut your finger or scrape a knee, a scab forms, allowing the skin underneath to regenerate and repair itself. The heart is not so lucky – it has very limited self-healing abilities. Instead, heart muscle cells damaged after a heart attack form scar tissue, making each heart beat less efficient. This condition can lead to chronic heart disease, the number one killer of both men and women in the US.

A mouse heart cell with 2 nuclei (blue) and Singheart RNA labelled by red fluorescent dyes.
Credit: A*STAR’s Genome Institute of Singapore

Research has shown that newborn mice retain the ability to completely regenerate and repair injuries to the heart because their heart muscle cells, or cardiomyocytes, are still able to divide and replenish damaged cells. But by adulthood, the mouse cardiomyocytes lose the ability to stimulate the necessary cell division processes. A research team in Singapore wondered what was preventing cardiomyocytes cell division in adult mice and if there was some way to lift that block.

This week in Nature Communications, they describe the identification of a molecule they call Singheart that may be the answer to their questions. Using tools that allow the analysis of gene activity in single cells revealed that a rare population of diseased cardiomyocytes are able to crank up genes related to cell division. And further analysis showed Singheart, a specialized genetic molecule called a long non-coding RNA, played a role in blocking this cell division gene.

As lead author Dr. Roger Foo, a principal investigator at Genome Institute of Singapore (GIS) and the National University Health System (NUHS), explained in a press release, these findings may lead to new self-healing strategies for heart disease,

“There has always been a suspicion that the heart holds the key to its own healing, regenerative and repair capability. But that ability seems to become blocked as soon as the heart is past its developmental stage. Our findings point to this potential block that when lifted, may allow the heart to heal itself.”