satisfying to see two projects you have supported for a long time do well. That’s
particularly true when the projects in question are targeting conditions that
have no other effective therapies.
This week we learned
that a clinical trial we funded to help people with spinal cord injuries
continues to show benefits. This trial holds a special place in our hearts
because it is an extension of the first clinical trial we ever funded.
Initially it was with Geron,
and was later taken up by Asterias
Biotherapeutics, which has seen been bought by Lineage Cell Therapeutics Inc.
The therapy involved transplanting oligodendrocyte progenitor cells (OPCs), which are derived from human embryonic stem cells, into people who suffered recent spinal cord injuries that left them paralyzed from the neck down. OPCs play an important role in supporting and protecting nerve cells in the central nervous system, the area damaged in a spinal cord injury. It’s hoped the cells will help restore some of the connections at the injury site, allowing patients to regain some movement and feeling.
In a news
release, Lineage said that its OPC
therapy continues to report positive results, “where the overall safety profile
of OPC1 has remained excellent with robust motor recovery in upper extremities
maintained through Year 2 patient follow-ups available to date.”
Two years in the
patients are all continuing to do well, and no serious unexpected side effects
have been seen. They also reported:
– Motor level improvements
Five of six Cohort 2 patients achieved
at least two motor levels of improvement over baseline on at least one side as
of their 24-month follow-up visit.
In addition, one Cohort 2 patient
achieved three motor levels of improvement on one side over baseline as of the
patient’s 24-month follow-up visit; improvement has been maintained through the
patient’s 36-month follow-up visit.
Brian M. Culley, CEO of Lineage Cell Therapeutics called the news “exciting”, saying “To put these improvements into perspective, a one motor level gain means the ability to move one’s arm, which contributes to the ability to feed and clothe oneself or lift and transfer oneself from a wheelchair. These are tremendously meaningful improvements to quality of life and independence.”
The other good news came from Orchard Therapeutics, a company we have
partnered with on a therapy for Severe Combined Immunodeficiency (SCID) also
known as “bubble baby diseases” (we have blogged about this a lot including
In a news
release Orchard announced that the European Medicines Agency (EMA) has granted an accelerated
assessment for their gene therapy for metachromatic leukodystrophy (MLD). This
is a rare and often fatal condition that results in the build-up of sulfatides
in the brain, liver, kidneys and other organs. Over time this makes it harder
and harder for the person to walk, talk, swallow or eat.
Anne Dupraz-Poiseau, chief regulatory
officer of Orchard Therapeutics, says this is testimony to the encouraging
early results of this therapy. “We look forward to working with the EMA to
ensure this potentially transformative new treatment, if approved, reaches
patients in the EU as quickly as possible, and continuing our efforts to expand
patient access outside the EU.”
The accelerated assessment potentially
provides a reduced review timeline from 210 to 150 days, meaning it could be
available to a wider group of patients sooner.
CIRM’s mission is very simple: to accelerate stem cell treatments to patients with unmet medical needs. Anne Klein’s son, Everett, was a poster boy for that statement. Born with a fatal immune disorder Everett faced a bleak future. But Anne and husband Brian were not about to give up. The following story is one Anne wrote for Parents magazine. It’s testament to the power of stem cells to save lives, but even more importantly to the power of love and the determination of a family to save their son.
My Son Was Born With ‘Bubble Boy’ Disease—But A Gene Therapy Trial Saved His Life
I wish more than anything that my son Everett had not been born with severe combined immunodeficiency (SCID). But I know he is actually one of the lucky unlucky ones. By Anne Klein
As a child in the ’80s, I watched a news story about David Vetter. David was known as “the boy in the bubble” because he was born with severe combined immunodeficiency (SCID), a rare genetic disease that leaves babies with very little or no immune system. To protect him, David lived his entire life in a plastic bubble that kept him separated from a world filled with germs and illnesses that would have taken his life—likely before his first birthday.
I was struck by David’s story. It was heartbreaking and seemed so otherworldly. What would it be like to spend your childhood in an isolation chamber with family, doctors, reporters, and the world looking in on you? I found it devastating that an experimental bone marrow transplant didn’t end up saving his life; instead it led to fatal complications. His mother, Carol Ann Demaret, touched his bare hand for the first and last time when he was 12 years old.
I couldn’t have known that almost 30 years later, my own son, Everett, would be born with SCID too.
Everett’s SCID diagnosis
At birth, Everett was big, beautiful, and looked perfectly healthy. My husband Brian and I already had a 2-and-a-half-year-old son, Alden, so we were less anxious as parents when we brought Everett home. I didn’t run errands with Alden until he was at least a month old, but Everett was out and about with us within a few days of being born. After all, we thought we knew what to expect.
But two weeks after Everett’s birth, a doctor called to discuss Everett’s newborn screening test results. I listened in disbelief as he explained that Everett’s blood sample indicated he may have an immune deficiency.
“He may need a bone marrow transplant,” the doctor told me.
I was shocked. Everett’s checkup with his pediatrician just two days earlier went swimmingly. I hung up and held on to the doctor’s assurance that there was a 40 percent chance Everett’s test result was a false positive.
After five grueling days of waiting for additional test results and answers, I received the call: Everett had virtually no immune system. He needed to be quickly admitted to UCSF Benioff Children’s Hospital in California so they could keep him isolated and prepare to give him a stem cell transplant. UCSF diagnosed him specifically with SCID-X1, the same form David battled.
Beginning SCID treatment
The hospital was 90 miles and more than two hours away from home. Our family of four had to be split into two, with me staying in the hospital primarily with Everett and Brian and Alden remaining at home, except for short visits. The sudden upheaval left Alden confused, shaken, and sad. Brian and I quickly transformed into helicopter parents, neurotically focused on every imaginable contact with germs, even the mildest of which could be life-threatening to Everett.
When he was 7 weeks old, Everett received a stem cell transplant with me as his donor, but the transplant failed because my immune cells began attacking his body. Over his short life, Everett has also spent more than six months collectively in the hospital and more than three years in semi-isolation at home. He’s endured countless biopsies, ultrasounds, CT scans, infusions, blood draws, trips to the emergency department, and medical transports via ambulance or helicopter.
Gene therapy to treat SCID
At age 2, his liver almost failed and a case of pneumonia required breathing support with sedation. That’s when a doctor came into the pediatric intensive care unit and said, “When Everett gets through this, we need to do something else for him.” He recommended a gene therapy clinical trial at the National Institutes of Health (NIH) that was finally showing success in patients over age 2 whose transplants had failed. This was the first group of SCID-X1 patients to receive gene therapy using a lentiviral vector combined with a light dose of chemotherapy.
After the complications from our son’s initial stem cell transplant, Brian and I didn’t want to do another stem cell transplant using donor cells. My donor cells were at war with his body and cells from another donor could do the same. Also, the odds of Everett having a suitable donor on the bone marrow registry were extremely small since he didn’t have one as a newborn. At the NIH, he would receive a transplant with his own, perfectly matched, gene-corrected cells. They would be right at home.
Other treatment options would likely only partially restore his immunity and require him to receive infusions of donor antibodies for life, as was the case with his first transplant. Prior gene therapy trials produced similarly incomplete results and several participants developed leukemia. The NIH trial was the first one showing promise in fully restoring immunity, without a risk of cancer. Brian and I felt it was Everett’s best option. Without hesitation, we flew across the country for his treatment. Everett received the gene therapy in September 2016 when he was 3, becoming the youngest patient NIH’s clinical trial has treated.
It’s been more than two years since Everett received gene therapy and now more than ever, he has the best hope of developing a fully functioning immune system. He just received his first vaccine to test his ability to mount a response. Now 6 years old, he’s completed kindergarten and has been to Disney World. He plays in the dirt and loves shows and movies from the ’80s (maybe some of the same ones David enjoyed).
Everett knows he has been through a lot and that his doctors “fixed his DNA,” but he’s focused largely on other things. He’s vocal when confronted with medical pain or trauma, but seems to block out the experiences shortly afterwards. It’s sad for Brian and me that Everett developed these coping skills at such a young age, but we’re so grateful he is otherwise expressive and enjoys engaging with others. Once in the middle of the night, he woke us up as he stood in the hallway, exclaiming, “I’m going back to bed, but I just want you to know that I love you with all my heart!”
I wish more than anything that Everett had not been born with such a terrible disease and I could erase all the trauma, isolation, and pain. But I know that he is actually one of the lucky unlucky ones. Everett is fortunate his disease was caught early by SCID newborn screening, which became available in California not long before his birth. Without this test, we would not have known he had SCID until he became dangerously ill. His prognosis would have been much worse, even under the care of his truly brilliant and remarkable doctors, some of whom cared for David decades earlier.
When Everett was 4, soon after the gene therapy gave him the immunity he desperately needed, our family was fortunate enough to cross paths with David’s mom, Carol Ann, at an Immune Deficiency Foundation event. Throughout my life, I had seen her in pictures and on television with David. In person, she was warm, gracious, and humble. When I introduced her to Everett and explained that he had SCID just like David, she looked at Everett with loving eyes and asked if she could touch him. As she touched Everett’s shoulder and they locked eyes, Brian and I looked on with profound gratitude.
Anne Klein is a parent, scientist, and a patient advocate for two gene therapy trials funded by the California Institute for Regenerative Medicine. She is passionate about helping parents of children with SCID navigate treatment options for their child.
At CIRM we are privileged to work with many remarkable people who combine brilliance, compassion and commitment to their search for new therapies to help people in need. One of those who certainly fits that description is UC Davis’ Jan Nolta.
This week the UC Davis Newsroom posted a great interview with Jan. Rather than try and summarize what she says I thought it would be better to let her talk for herself.
Talking research, unscrupulous clinics, and sustaining the momentum
In 2007, Jan Nolta
returned to Northern California from St. Louis to lead what was at the
time UC Davis’ brand-new stem cell program. As director of the UC Davis Stem Cell Program
and the Institute for Regenerative Cures, she has overseen the opening
of the institute, more than $140 million in research grants, and dozens
upon dozens of research studies. She recently sat down to answer some
questions about regenerative medicine and all the work taking place at UC Davis Health.
Q: Turning stem cells into cures has been your mission and mantra since you founded the program. Can you give us some examples of the most promising research?
I am so excited about our research. We have about 20 different disease-focused teams.
That includes physicians, nurses, health care staff, researchers and
faculty members, all working to go from the laboratory bench to
patient’s bedside with therapies.
Perhaps the most promising and
exciting research right now comes from combining blood-forming
stem cells with gene therapy. We’re working in about
eight areas right now, and the first cure, something that we definitely
can call a stem cell “cure,” is coming from this combined approach.
doctors will be able to prescribe this type of stem cell therapy.
Patients will use their own bone marrow or umbilical cord stem cells.
Teams such as ours, working in good manufacturing practice
facilities, will make vectors, essentially “biological delivery
vehicles,” carrying a good copy of the broken gene. They will be
reinserted into a patient’s cells and then infused back into the
patient, much like a bone marrow transplant.
“Perhaps the most promising and exciting research right now comes from combining blood-forming stem cells with gene therapy.”
Along with treating the famous bubble baby disease,
where I had started my career, this approach looks very promising for
sickle cell anemia. We’re hoping to use it to treat several different
inherited metabolic diseases. These are conditions characterized by an
abnormal build-up of toxic materials in the body’s cells. They interfere
with organ and brain function. It’s caused by just a single enzyme.
Using the combined stem cell gene therapy, we can effectively put a good
copy of the gene for that enzyme back into a patient’s bone marrow stem
cells. Then we do a bone marrow transplantation and bring back a
person’s normal functioning cells.
The beauty of this therapy is
that it can work for the lifetime of a patient. All of the blood cells
circulating in a person’s system would be repaired. It’s the number one
stem cell cure happening right now. Plus, it’s a therapy that won’t be
rejected. These are a patient’s own stem cells. It is just one type of
stem cell, and the first that’s being commercialized to change cells
throughout the body.
Q: Let’s step back for a moment. In 2004, voters approved Proposition 71.
It has funded a majority of the stem cell research here at UC Davis and
throughout California. What’s been the impact of that ballot measure
and how is it benefiting patients?
We have learned so
much about different types of stem cells, and which stem cell will be
most appropriate to treat each type of disease. That’s huge. We had to
first do that before being able to start actual stem cell therapies. CIRM [California Institute for Regenerative Medicine] has funded Alpha Stem Cell Clinics.
We have one of them here at UC Davis and there are only five in the
entire state. These are clinics where the patients can go for
high-quality clinical stem cell trials approved by the FDA
[U.S. Food and Drug Administration]. They don’t need to go to
“unapproved clinics” and spend a lot of money. And they actually
“By the end of this year, we’ll have 50 clinical trials.”
By the end of this year, we’ll have 50 clinical trials [here at UC Davis Health]. There are that many in the works.
Our Alpha Clinic
is right next to the hospital. It’s where we’ll be delivering a lot of
the immunotherapies, gene therapies and other treatments. In fact, I
might even get to personally deliver stem cells to the operating room
for a patient. It will be for a clinical trial involving people who have
broken their hip. It’s exciting because it feels full circle, from
working in the laboratory to bringing stem cells right to the patient’s
We have ongoing clinical trials
for critical limb ischemia, leukemia and, as I mentioned, sickle cell
disease. Our disease teams are conducting stem cell clinical trials
targeting sarcoma, cellular carcinoma, and treatments for dysphasia [a
swallowing disorder], retinopathy [eye condition], Duchenne muscular
dystrophy and HIV. It’s all in the works here at UC Davis Health.
also great potential for therapies to help with renal disease and
kidney transplants. The latter is really exciting because it’s like a
mini bone marrow transplant. A kidney recipient would also get some
blood-forming stem cells from the kidney donor so that they can better
accept the organ and not reject it. It’s a type of stem cell therapy
that could help address the burden of being on a lifelong regime of
immunosuppressant drugs after transplantation.
Q: You and
your colleagues get calls from family members and patients all the
time. They frequently ask about stem cell “miracle” cures. What should
people know about unproven treatments and unregulated stem cell clinics?
That’s a great question.The number one rule is that if
you’re asked to pay money for a stem cell treatment, don’t do it. It’s a
big red flag.
When it comes to advertised therapies: “The number one rule is that if you’re asked to pay money for a stem cell treatment, don’t do it. It’s a big red flag.”
there are unscrupulous people out there in “unapproved clinics” who
prey on desperate people. What they are delivering are probably not even
stem cells. They might inject you with your own fat cells, which
contain very few stem cells. Or they might use treatments that are not
matched to the patient and will be immediately rejected. That’s
dangerous. The FDA is shutting these unregulated clinics down one at a
time. But it’s like “whack-a-mole”: shut one down and another one pops
On the other hand, the Alpha Clinic is part of our
mission is to help the public get to the right therapy, treatment or
clinical trial. The big difference between those who make patients pay
huge sums of money for unregulated and unproven treatments and UC Davis
is that we’re actually using stem cells. We produce them in rigorously
regulated cleanroom facilities. They are certified to contain at least 99% stem cells.
and family members can always call us here. We can refer them to a
genuine and approved clinical trial. If you don’t get stem cells at the
beginning [of the clinical trial] because you’re part of the placebo
group, you can get them later. So it’s not risky. The placebo is just
saline. I know people are very, very desperate. But there are no miracle
cures…yet. Clinical trials, approved by the FDA, are the only way we’re
going to develop effective treatments and cures.
Scientific breakthroughs take a lot of patience and time. How do you and
your colleagues measure progress and stay motivated?
Motivation? “It’s all for the patients.”
all for the patients. There are not good therapies yet for many
disorders. But we’re developing them. Every day brings a triumph.
Measuring progress means treating a patient in a clinical trial, or
developing something in the laboratory, or getting FDA approval. The big
one will be getting biological license approval from the FDA, which
means a doctor can prescribe a stem cell or gene therapy treatment. Then
it can be covered by a patient’s health insurance.
I’m a cancer
survivor myself, and I’m also a heart patient. Our amazing team here at
UC Davis has kept me alive and in great health. So I understand it from
both sides. I understand the desperation of “Where do I go?” and “What
do I do right now?” questions. I also understand the science side of
things. Progress can feel very, very slow. But everything we do here at
the Institute for Regenerative Cures is done with patients in mind, and
We know that each day is so important when you’re watching
a loved one suffer. We attend patient events and are part of things
like Facebook groups, where people really pour their hearts out. We say
to ourselves, “Okay, we must work harder and faster.” That’s our
motivation: It’s all the patients and families that we’re going to help
who keep us working hard.
But then came news that another big name celebrity, in this case Star Trek star William Shatner, was going to one of these clinics for an infusion of what he called “restorative cells”.
It’s a reminder that
for every step forward we take in trying to educate the public about the
dangers of clinics offering unproven therapies, we often take another step back
when a celebrity essentially endorses the idea.
So that’s why we are
taking our message directly to the people, as often as we can and wherever we
In June we are going
to be holding a free, public event in Los Angeles to coincide with the opening
of the International Society for Stem Cell Research’s Annual Conference, the
biggest event on the global stem cell calendar. There’s still time to register for that by the way. The event is from 6-7pm on
Tuesday, June 25th in Petree Hall C., at the Los Angeles Convention
Center at 1201 South Figueroa Street, LA 90015.
It’s going to be an
opportunity to learn about the real progress being made in stem cell research,
thanks in no small part to CIRM’s funding. We’re honored to be joined by UCLA’s
Dr. Don Kohn, who has helped cure dozens of children born with a fatal immune
system disorder called severe combined immunodeficiency, also known as “bubble
baby disease”. And we’ll hear from the family of one of those children whose
life he helped save.
And because CIRM is
due to run out of money to fund new projects by the end of this year you’ll
also learn about the very real concerns we have about the future of stem cell
research in California and what can be done to address those concerns. It promises
to be a fascinating evening.
But that’s not all. Our
partners at USC will be holding another public event on stem cell research, on
Wednesday June 26th from 6.30p to 8pm. This one is focused on
treatments for age-related blindness. This features some of the top stem cell
scientists in the field who are making encouraging progress in not just slowing
down vision loss, but in some cases even reversing it.
We know that we face
some serious challenges in trying to educate people about the risks of going to
a clinic offering unproven therapies. But we also know we have a great story to
tell, one that shows how we are already changing lives and saving lives, and
that with the support of the people of California we’ll do even more in the
years to come.
Our immune system is an important and essential part of everyday life. It is crucial for fighting off colds and, with the help of vaccinations, gives us immunity to potentially lethal diseases. Unfortunately, for some infants, this innate bodily defense mechanism is not present or is severely lacking in function.
This condition is known as severe combined immunodeficiency (SCID), commonly nicknamed “bubble baby” disease because of the sterile plastic bubble these infants used to be placed in to prevent exposure to bacteria, viruses, and fungi that can cause infection. There are several forms of SCID, one of which involves a single genetic mutation on the X chromosome and is known as SCID-X1
Many infants with SCID-X1 develop chronic diarrhea, a fungal infection called thrush, and skin rashes. Additionally, these infants grow slowly in comparison to other children. Without treatment, many infants with SCID-X1 do not live beyond infancy.
SCID-X1 occurs almost predominantly in males since they only carry one X chromosome, with at least 1 in 50,000 baby boys born with this condition. Since females carry two X chromosomes, one inherited from each parent, they are unlikely to inherit two X chromosomes with the mutation present since it would require the father to have SCID-X1.
What if there was a way to address this condition by correcting the single gene mutation? Dr. Matthew Porteus at Stanford University is leading a study that has developed an approach to treat SCID-X1 that utilizes this concept.
By using CRISPR-Cas9 technology, which we have discussed in detail in a previous blog post, it is possible to delete a problematic gene and insert a corrected gene. Dr. Porteus and his team are using CRISPR-Cas9 to edit blood stem cells, which give rise to immune cells, which are the foundation of the body’s defense mechanism. In a study published in Nature, Dr. Porteus and his team have demonstrated proof of concept of this approach in an animal model.
The Stanford team was able to take blood stem cells from six infants with SCID-X1 and corrected them with CRISPR-Cas9. These corrected stem cells were then introduced into mice modeled to have SCID-X1. It was found that these mice were not only able to make immune cells, but many of the edited stem cells maintained their ability to continuously create new blood cells.
In a press release, Dr. Mara Pavel-Dinu, a member of the research team, said:
“To our knowledge, it’s the first time that human SCID-X1 cells edited with CRISPR-Cas9 have been successfully used to make human immune cells in an animal model.”
CIRM has previously awarded Dr. Porteus with a preclinical development award aimed at developing gene correction therapy for blood stem cells for SCID-X1. In addition to this, CIRM has funded two other projects conducted by Dr. Porteus related to CRISPR-Cas9. One of these projects used CRISPR-Cas 9 to develop a treatment for chronic sinusitis due to cystic fibrosis and the second project used the technology to develop an approach for treating sickle cell disease.
CIRM has also funded four clinical trials related to SCID. Two of these trials are related to SCID-X1, one being conducted at St. Jude Children’s Research Hospital and the other at Stanford University. The third trial is related to a different form of SCID known as ADA-SCID and is being conducted at UCLA in partnership with Orchard Therapeutics. Finally, the last of the four trials is related to an additional form of SCID known as ART-SCID and is being conducted at UCSF.
There are more than 200,000 cases of traumatic brain injury (TBI) in the US every year. The injuries can be devastating, resulting in everything from difficult sleeping to memory loss, depression and severe disability. There is no cure. But this week the SanBio Group had some encouraging news from its Phase 2 STEMTRA clinical trial.
In the trial patients with TBI were given stem cells, derived from the bone marrow of healthy adult donors. When transplanted into the area of injury in the brain, these cells appear to promote recovery by stimulating the brain’s own regenerative ability.
In this trial the cells demonstrated what the company describes as “a statistically significant improvement in their motor function compared to the control group.”
Endometriosis is an often painful condition that is caused when the cells that normally line the inside of the uterus grow outside of it, causing scarring and damaging other tissues. Over time it can result in severe pain, infertility and increase a woman’s risk for ovarian cancer.
There is no effective long-term treatment but now researchers at Northwestern Medicine have developed an approach, using the woman’s own cells, that could help treat the problem.
The researchers took cells from women, turned them into iPS pluripotent stem cells and then converted those into healthy uterine cells. In laboratory tests these cells responded to the progesterone, the hormone that plays a critical role in the uterus.
In a news release, Dr. Serdar Bulun, a senior author of the study, says this opens the way to testing these cells in women:
“This is huge. We’ve opened the door to treating endometriosis. These women with endometriosis start suffering from the disease at a very early age, so we end up seeing young high school girls getting addicted to opioids, which totally destroys their academic potential and social lives.”
A lot of the research we write about on the Stem Cellar focuses on potential treatments or new approaches that show promise. So every once in a while, it’s good to remind ourselves that there are already stem cell treatments that are not just showing promise, they are saving lives.
That is the case with Ja’Ceon Golden. Regular readers of our blog know that Ja’Ceon was diagnosed with Severe Combined Immunodeficiency (SCID) also known as “bubble baby disease” when he was just a few months old. Children born with SCID often die in the first few years of life because they don’t have a functioning immune system and so even a simple infection can prove life-threatening.
Today he is a healthy, happy, thriving young boy. These pictures, taken by his great aunt Dannie Hawkins, including one of him in his Halloween costume, show how quickly he is growing. And all thanks to some amazing researchers, an aunt who wouldn’t give up on him, and the support of CIRM.
“We were so desperate. When we heard about this treatment were willing to do anything to come here.”
In the above quote from Zahraa El Kerdi, “here” refers to UCLA, a world away from her hometown in Lebanon. In September 2015, Zahree gave birth to a son, Hussein, who appeared perfectly healthy. But by six months, he was barely clinging to life due to an inherited blood disorder, ADA-SCID, also called Bubble Baby disease. The disorder left Hussein without a functioning immune system so even a common cold could prove deadly. In fact, SCID babies rarely survive past one year of age. Up until now, no treatment options existed for the disease.
With before and after scenes of Hussein’s treatment as well as animation describing how the therapy works, the short documentary is equal parts heart wrenching, uplifting and educational. Basically, what I’m trying to say is, it’s a must-see and available to view above.
Ronnie Kashyap, patient in SCID clinical trial: Photo Pawash Priyank
More than 35 million people around the world have been killed by HIV, the virus that causes AIDS. So, it’s hard to think that the same approach the virus uses to infect cells could also be used to help children battling a deadly immune system disorder. But that’s precisely what researchers at UC San Francisco and St. Jude Children’s Research Hospital are doing.
The disease the researchers are tackling is a form of severe combined immunodeficiency (SCID). It’s also known as ‘bubble baby’ disease because children are born without a functioning immune system and in the past were protected from germs within the sterile environment of a plastic bubble. Children with this disease often die of infections, even from a common cold, in the first two years of life.
The therapy involves taking the patient’s own blood stem cells from their bone marrow, then genetically modifying them to correct the genetic mutation that causes SCID. The patient is then given low-doses of chemotherapy to create space in their bone marrow for the news cells. The gene-corrected stem cells are then transplanted back into the infant, creating a new blood supply and a repaired immune system.
Unique delivery system
The novel part of this approach is that the researchers are using an inactivated form of HIV as a means to deliver the correct gene into the patient’s cells. It’s well known that HIV is perfectly equipped to infiltrate cells, so by taking an inactivated form – meaning it cannot infect the individual with HIV – they are able to use that infiltrating ability for good.
The researchers say seven infants treated and followed for up to 12 months, have all produced the three major immune system cell types affected by SCID. In a news release, lead author Ewelina Mamcarz, said all the babies appear to be doing very well:
“It is very exciting that we observed restoration of all three very important cell types in the immune system. This is something that’s never been done in infants and a huge advantage over prior trials. The initial results also suggest our approach is fundamentally safer than previous attempts.”
If the stem cell-gene therapy combination continues to show it is both safe and effective it would be a big step forward in treating SCID. Right now, the best treatment is a bone marrow transplant, but only around 20 percent of infants with SCID have a sibling or other donor who is a good match. The other 80 percent have to rely on a less well-matched bone marrow transplant – usually from a parent – that can still leave the child prone to life-threatening infections or potentially fatal complications such as graft-versus-host disease.
CIRM is funding two other clinical trials targeting SCID. You can read about them here and here.
Welcome back to our “Throwback Thursday” series on the Stem Cellar. Over the years, we’ve accumulated an arsenal of exciting stem cell stories about advances towards stem cell-based cures for serious diseases. Today we’re featuring stories about the progress of CIRM-funded clinical trials for the treatment of a devastating, usually fatal, primary immune disease that strikes newborn babies.
Evie, a former “bubble baby” enjoying life by playing inside a giant plastic bubble
‘Bubble baby disease’ will one day be a thing of the past. That’s a bold statement, but I say it with confidence because of the recent advancements in stem cell gene therapies that are curing infants of this life-threatening immune disease.
The scientific name for ‘bubble baby disease’ is severe combined immunodeficiency (SCID). It prevents the proper development of important immune cells called B and T cells, leaving newborns without a functioning immune system. Because of this, SCID babies are highly susceptible to deadly infections, and without treatment, most of these babies do not live past their first year. Even a simple cold virus can be fatal.
Scientists are working hard to develop stem cell-based gene therapies that will cure SCID babies in their first months of life before they succumb to infections. The technology involves taking blood stem cells from a patient’s bone marrow and genetically correcting the SCID mutation in the DNA of these cells. The corrected stem cells are then transplanted back into the patient where they can grow and regenerate a healthy immune system. Early-stage clinical trials testing these stem cell gene therapies are showing very encouraging results. We’ll share a few of these stories with you below.
CIRM-funded trials for SCID
CIRM is funding three clinical trials, one from UCLA, one at Stanford and one from UCSF & St. Jude Children’s Research Hospital, that are treating different forms of SCID using stem cell gene therapies.
Adenosine Deaminase-Deficient SCID
The first trial is targeting a form of the disease called adenosine deaminase-deficient SCID or ADA-SCID. Patients with ADA-SCID are unable to make an enzyme that is essential for the function of infection-fighting immune cells called lymphocytes. Without working lymphocytes, infants eventually are diagnosed with SCID at 6 months. ADA-SCID occurs in approximately 1 in 200,000 newborns and makes up 15% of SCID cases.
CIRM is funding a Phase 2 trial for ADA-SCID that is testing a stem cell gene therapy called OTL-101 developed by Dr. Don Kohn and his team at UCLA and a company called Orchard Therapeutics. 10 patients were treated in the trial, and amazingly, nine of these patients were cured of their disease. The 10th patient was a teenager who received the treatment knowing that it might not work as it does in infants. You can read more about this trial in our blog from earlier this year.
In a recent news release, Orchard Therapeutics announced that the US Food and Drug Administration (FDA) has awarded Rare Pediatric Disease Designation to OTL-101, meaning that the company will qualify for priority review for drug approval by the FDA. You can read more about what this designation means in this blog.
The second SCID trial CIRM is funding is treating patients with X-linked SCID. These patients have a genetic mutation on a gene located on the X-chromosome that causes the disease. Because of this, the disease usually affects boys who have inherited the mutation from their mothers. X-linked SCID is the most common form of SCID and appears in 1 in 60,000 infants.
UCSF and St. Jude Children’s Research Hospital are conducting a Phase 1/2 trial for X-linked SCID. The trial, led by Dr. Brian Sorrentino, is transplanting a patient’s own genetically modified blood stem cells back into their body to give them a healthy new immune system. Patients do receive chemotherapy to remove their diseased bone marrow, but doctors at UCSF are optimizing low doses of chemotherapy for each patient to minimize any long-term effects. According to a UCSF news release, the trial is planning to treat 15 children over the next five years. Some of these patients have already been treated and we will likely get updates on their progress next year.
CIRM is also funding a third clinical trial out of Stanford University that is hoping to make bone marrow transplants safer for X-linked SCID patients. The team, led by Dr. Judy Shizuru, is developing a therapy that will remove unhealthy blood stem cells from SCID patients to improve the survival and engraftment of healthy bone marrow transplants. You can read more about this trial on our clinical trials page.
SCID Patients Cured by Stem Cells
These clinical trial results are definitely exciting, but what is more exciting are the patient stories that we have to share. We’ve spoken with a few of the families whose children participated in the UCLA and UCSF/St. Jude trials, and we asked them to share their stories so that other families can know that there is hope. They are truly inspiring stories of heartbreak and joyful celebration.
Evie is a now six-year-old girl who was diagnosed with ADA-SCID when she was just a few months old. She is now cured thanks to Don Kohn and the UCLA trial. Her mom gave a very moving presentation about Evie’s journey at the CIRM Bridges Trainee Annual Meeting this past July. You can watch the 20-minute talk below:
Ronnie: Photo courtesy Pawash Priyank
Ronnie, who is still less than a year old, was diagnosed with X-linked SCID just days after he was born. Luckily doctors told his parents about the UCSF/St. Jude trial and Ronnie was given the life-saving stem cell gene therapy before he was six months old. Now Ronnie is building a healthy immune system and is doing well back at home with his family. Ronnie’s dad Pawash shared his families moving story at our September Board meeting and you can watch it here.
Our mission at CIRM is to accelerate stem cell treatments to patients with unmet medical needs. We hope that by funding promising clinical trials like the ones mentioned in this blog, that one day soon there will be approved stem cell therapies for patients with SCID and other life-threatening diseases.
Today, in a new video, I highlight a brave young patient, Ronnie, and his parents who decided to participate in a CIRM-funded clinical trial run by St. Jude Children’s Research Hospital and UC San Francisco in an attempt to save Ronnie’s life from an often-fatal disease called severe combined immunodeficiency (SCID). This disorder, also known as bubble baby disease, leaves newborns without a functioning immune system which can turn a simple cold into a potentially deadly infection.
Watch this story’s happy ending in the video above.