A study published in the New England Journal of Medicine shows that an experimental form of stem cell and gene therapy has cured 48 of 50 children born with a deadly condition called ADA-SCID.
Children with ADA-SCID, (severe combined immunodeficiency due to adenosine deaminase deficiency) lack a key enzyme that is essential for a healthy, functioning immune system. As a result, even a simple infection could prove fatal to these children and, left untreated, most will die within the first two years of life.
In the study, part of which was supported by CIRM, researchers at the University of California Los Angeles (UCLA) and Great Ormond Street Hospital (GOSH) in London took some of the children’s own blood-forming stem cells and, in the lab, corrected the genetic mutation that causes ADA-SCID. They then returned those cells to the children. The hope was that over time the corrected stem cells would create a new blood supply and repair the immune system.
In the NEJM study the researchers reported outcomes for the children two and three years post treatment.
“Between all three clinical trials, 50 patients were treated, and the overall results were very encouraging,” said Dr. Don Kohn, a distinguished professor of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “All the patients are alive and well, and in more than 95% of them, the therapy appears to have corrected their underlying immune system problems.”
Two of the children did not respond to the therapy and both were returned to the current standard-of-care therapy. One subsequently underwent a bone marrow transplant. None of the children in the study experienced serious side-effects.
“This is encouraging news for all families affected by this rare but deadly condition,” says Maria T. Millan, MD, President and CEO of CIRM. “It’s also a testament to the power of persistence. Don Kohn has been working on developing this kind of therapy for 35 years. To see it paying off like this is a remarkable testament to his skill as a researcher and determination to help these patients.”
On March 19th we held a special Facebook Live “Ask the Stem Cell Team About Autism” event. We were fortunate enough to have two great experts – Dr. Alysson Muotri from UC San Diego, and CIRM’s own Dr. Kelly Shepard. As always there is a lot of ground to cover in under one hour and there are inevitably questions we didn’t get a chance to respond to. So, Dr. Shepard has kindly agreed to provide answers to all the key questions we got on the day.
If you didn’t get a chance to see the event you can watch the video here. And feel free to share the link, and this blog, with anyone you think might be interested in the material.
Can umbilical cord blood stem cells help reduce some of the symptoms?
This question was addressed by Dr. Muotri in the live presentation. To recap, a couple of clinical studies have been reported from scientists at Duke University and Sutter Health, but the results are not universally viewed as conclusive. The Duke study, which focused on very young children, reported some improvements in behavior for some of the children after treatment, but it is important to note that this trial had no placebo control, so it is not clear that those patients would not have improved on their own. The Duke team has moved forward with larger trial and placebo control.
Does it have to be the child’s own cord blood or could donated blood work too?
In theory, a donated cord product could be used for similar purposes as a child’s own cord, but there is a caveat- the donated cord tissues must have some level of immune matching with the host in order to not be rejected or lead to other complications, which under certain circumstances, could be serious.
Some clinics claim that the use of fetal stem cells can help stimulate improved blood and oxygen flow to the brain. Could that help children with autism?
Fetal stem cells have been tested in FDA approved/sanctioned clinical trials for certain brain conditions such as stroke and Parkinson Disease, where there is clearer understanding of how and which parts of the brains are affected, which nerve cells have been lost or damaged, and where there is a compelling biological rationale for how certain properties the transplanted cells, such as their anti-inflammatory properties, could provide benefit.
In his presentation, Dr. Muotri noted that neurons are not lost in autistic brains, so there is nothing that would be “replaced” by such a treatment. And although some forms of autism might include inflammation that could potentially be mitigated, it is unlikely that the degree of benefit that might come from reducing inflammation would be worth the risks of the treatment, which includes intracranial injection of donated material. Unfortunately, we still do not know enough about the specific causes and features of autism to determine if and to what extent stem cell treatments could prove helpful. But we are learning more every day, especially with some of the new technologies and discoveries that have been enabled by stem cell technology.
Some therapies even use tissue from sheep claiming that a pill containing sheep pancreas can migrate to and cure a human pancreas, pills containing sheep brains can help heal human brains. What are your thoughts on those?
For some conditions, there may be a scientific rationale for how a specific drug or treatment could be delivered orally, but this really depends on the underlying biology of the condition, the means by which the drug exerts its effect, and how quickly that drug or substance will be digested, metabolized, or cleared from the body’s circulation. Many drugs that are delivered orally do not reach the brain because of the blood-brain barrier, which serves to isolate and protect the brain from potentially harmful substances in the blood circulation. For such a drug to be effective, it would have to be stable within the body for a period of time, and be something that could exert its effects on the brain either directly or indirectly.
Sheep brain or pancreas (or any other animal tissue consumed) in a pill form would be broken down into basic components immediately by digestion, i.e. amino acids, sugars, much like any other meat or food. Often complex treatments designed to be specifically targeted to the brain are delivered by intra-cranial/intrathecal injection, or by developing special strategies to evade the blood brain barrier, a challenge that is easier said than done. For autism, there is still a lot to be learned regarding how a therapeutic intervention might work to help people, so for now, I would caution against the use of dietary supplements or pills that are not prescribed or recommended by your doctor.
What are the questions parents should ask before signing up for any stem cell therapy
When you have a great story to tell the best and most effective way to get it out to the widest audience is still the media, both traditional mainstream and new social media. Recently we have seen three great examples of how that can be done and, hopefully, the benefits that can come from it.
First, let’s go old
school. Earlier this month Caroline Chen wrote a wonderful
in-depth article about clinics that are cashing in on a gray area in stem
cell research. The piece, a collaboration between the New Yorker magazine and
ProPublica, focused on the use of amniotic stem cell treatments and the gap
between what the clinics who offer it are claiming it can do, and the reality.
Here’s one paragraph
profiling a Dr. David Greene, who runs a company providing amniotic fluid to
clinics. It’s a fine piece of writing showing how the people behind these
therapies blur the lines between fact and reality, not just about the cells but
also about themselves:
“Greene said that amniotic stem cells derive their healing power from an ability to develop into any kind of tissue, but he failed to mention that mainstream science does not support his claims. He also did not disclose that he lost his license to practice medicine in 2009, after surgeries he botched resulted in several deaths. Instead, he offered glowing statistics: amniotic stem cells could help the heart beat better, “on average by twenty per cent,” he said. “Over eighty-five per cent of patients benefit exceptionally from the treatment.”
backpedals on that claim, saying:
“I don’t claim that this is a treatment. I don’t claim that it cures anything. I don’t claim that it’s a permanent fix. All I discuss is maybe, potentially, people can get some improvements from stem-cell care.”
This week CBS2
TV in Chicago did their own investigative story about how the number of local
clinics offering unproven and unapproved therapies is on the rise. Reporter Pam
Zekman showed how misleading newspaper ads brought in people desperate for
something, anything, to ease their arthritis pain.
She interviewed two
patients who went to one of those clinics, and ended up out of pocket, and out
“They said they would regenerate the cartilage,” Patricia Korona recalled. She paid $4500 for injections in her knee, but the pain continued. Later X-rays were ordered by her orthopedic surgeon.
“He found bone on bone,” Korona said. “No cartilage grew, which tells me it failed; didn’t work.”
John Zapfel paid $14,000 for stem cell injections on each side of his neck and his shoulder. But an MRI taken by his current doctor showed no improvement.
“They ripped me off, and I was mad.” Zapfel said.
TV and print reports
like this are a great way to highlight the bogus claims made by many of these
clinics, and to shine a light on how they use hype to sell hope to people who
are in pain and looking for help.
At a time when
journalism seems to be increasingly under attack with accusations of “fake news”
it’s encouraging to see reporters like these taking the time and news outlets
devoting the resources to uncover shady practices and protect vulnerable
But the news isn’t
all bad, and the use of social media can help highlight the good news.
That’s what happened
yesterday in our latest CIRM
Facebook Live “Ask the Stem Cell Team” event. The event focused on the
future of stem cell research but also included a really thoughtful look at the
progress that’s been made over the last 10-15 years.
We had two great
guests, UC Davis stem cell researcher and one of the leading bloggers on the
field, Paul Knoepfler PhD; and David
Higgins, PhD, a scientist, member of the CIRM Board and a Patient Advocate
for Huntington’s Disease. They were able to highlight the challenges of the
early years of stem cell research, both globally and here at CIRM, and show how
the field has evolved at a remarkable rate in recent years.
subject of the “bogus clinics” came up – Paul has become a national expert on
these clinics and is quoted in the New Yorker article – as did the subject of
the frustration some people feel at what they consider to be the too-slow pace
of progress. As David Higgins noted, we all think it’s too slow, but we are not
going to race recklessly ahead in search of something that might heal if we
might also end up doing something that might kill.
A portion of the
discussion focused on funding and, in particular, what happens if CIRM is no
longer around to fund the most promising research in California. We are due to
run out of funding for new projects by the end of this year, and without a
re-infusion of funds we will be pretty much closing our doors by the end of
2020. Both Paul and David felt that could be disastrous for the field here in
California, depriving the most promising projects of support at a time when
they needed it most.
It’s probably not
too surprising that three people so closely connected to CIRM (Paul has
received funding from us in the past) would conclude that CIRM is needed for
stem cell research to not just survive but thrive in California.
A word of caution
before you watch: fashion conscious people may be appalled at how my pocket handkerchief
took on a life of its own.
Former San Francisco Mayor and California State Assembly Speaker Willie Brown is many things, but shy is not one of them. A profile of him in the San Francisco Chronicle once described him as “Brash, smart, confident”. But for years Da Mayor – as he is fondly known in The City – said very little about a condition that is slowly destroying his vision. Mayor Brown has retinitis pigmentosa (RP).
RP is a degenerative disease that slowly destroys a person’s sight vision by attacking and destroying photoreceptors in the retina, the light-sensitive area at the back of the eye that is critical for vision. At a recent conference held by the Everylife Foundation for Rare Diseases, Mayor Brown gave the keynote speech and talked about his life with RP.
He described how people thought he was being rude because he would walk by them on the streets and not say hello. The truth is, he couldn’t see them.
He was famous for driving fancy cars like Bentleys, Maseratis and Ferraris. When he stopped doing that, he said, “people thought I was broke because I no longer had expensive cars.” The truth is his vision was too poor for him to drive.
Despite its impact on his life RP hasn’t slowed Da Mayor down, but now there’s a new clinical trial underway that might help him, and others like him, regain some of that lost vision.
The trial is the work of Dr. Henry Klassen at the University of California, Irvine (UCI). Dr. Klassen just announced the treatment of their first four patients, giving them stem cells that hopefully will slow down or even reverse the progression of RP.
“We are delighted to be moving into the clinic after many years of bench research,” Klassen said in a news release.
The patients were each given a single injection of retinal progenitor cells. It’s hoped these cells will help protect the photoreceptors in the retina that have not yet been damaged by RP, and even revive those that have become impaired but not yet destroyed by the disease.
The trial will enroll 16 patients in this Phase 1 trial. They will all get a single injection of retinal cells into the eye most affected by the disease. After that, they’ll be followed for 12 months to make sure that the therapy is safe and to see if it has any beneficial effects on vision in the treated eye, compared to the untreated one.
In a news release Jonathan Thomas, Ph.D., J.D., Chair of the CIRM Board said it’s always exciting when a therapy moves out of the lab and into people:
“This is an important step for Dr. Klassen and his team, and hopefully an even more important one for people battling this devastating disease. Our mission at CIRM is to accelerate the development of stem cell therapies for patients with unmet medical needs, and this certainly fits that bill. That’s why we have invested almost $19 million in helping this therapy reach this point.”
RP hasn’t defeated Da Mayor. Willie Brown is still known as a sharp dresser and an even sharper political mind. His message to the people at the Everylife Foundation conference was, “never give up, keep striving, keep pushing, keep hoping.”
To learn more about the study or to enroll contact the UCI Alpha Stem Cell Clinic at 949-824-3990 or by email at firstname.lastname@example.org.
Process is not a sexy word. No one gets excited thinking about improving a process. Yet behind every great idea, behind every truly effective program is someone who figured out a way to improve the process, to make that idea not just work, but work better.
It’s not glamorous. Sometimes it’s not even pretty. But it is essential.
Yesterday in Oakland our governing Board approved two new concepts to improve our process, to help us fund research in a way that is faster, smarter and ultimately helps us better meet our mission of accelerating the development of stem cell therapies for patients with unmet medical needs.
The new concepts are for Discovery – the earliest stage of research – and the Translational phase, a critical step in moving promising therapies out of the lab and toward clinical trials where they can be tested in people.
In a news release C. Randal Mills, Ph.D., CIRM’s President and CEO, said that these additions built on the work started when the agency launched CIRM 2.0 in January for the clinical phase of research:
“What makes this approach different is that under CIRM 2.0 we are creating a pathway for research, from Discovery to Translational and Clinical, so that if a scientist is successful with their research at one level they are able to move that ahead into the next phase. We are not interested in research just for its own sake. We are interested in research that is going to help us help patients.”
In the Discovery program, for example, we will now be able to offer financial incentives to encourage researchers who successfully complete their work to move it along into the Translational phase – either themselves or by finding a scientific partner willing to take it up and move it forward.
This does a number of things. First it helps create a pipeline for the most promising projects so ideas that in the past might have stopped once the initial study ended now have a chance to move forward. Obviously our hope is that this forward movement will ultimately lead to a clinical trial. That won’t happen with every research program we fund but this approach will certainly increase the possibility that it might.
There’s another advantage too. By scheduling the Discovery and Translational awards more regularly we are creating a grant system that has more predictability, making it easier for researchers to know when they can apply for funding.
We estimate that each year there will be up to 50 Discovery awards worth a total of $53 million; 12 Translation awards worth a total of $40 million; and 12 clinical awards worth around $100 million. That’s a total of more than $190 million every year for research.
This has an important advantage for the stem cell agency too. We have close to $1 billion left in the bank so we want to make sure we spend it as wisely as we can.
As Jonathan Thomas, Ph.D. J.D, the Chair of our Board, said, having this kind of plan helps us better plan our financial future;
“Knowing how often these programs are going to be offered, and how much money is likely to be awarded means the Board has more information to work with in making decisions on where best to allocate our funding.”
The Board also renewed funding for both the Bridges and SPARK (formerly Creativity) programs. These are educational and training programs aimed at developing the next generation of stem cell scientists. The Bridges students are undergraduate or Master’s level students. The SPARK students are all still in high school. Many in both groups come from poor or low-income communities. This program gives them a chance to work in a world-class stem cell research facility and to think about a career in science, something that for many might have been unthinkable without Bridges or SPARK.
Process isn’t pretty. But for the students who can now think about becoming a scientist, for the researchers who can plan new studies, and for the patients who can now envision a potential therapy getting into clinical trials, that process can make all the difference.
There is power in a single voice. I am always reminded of that whenever I meet a patient advocate and hear them talk about the need for treatments and cures – and not just for their particular disease but for everyone.
The passion and commitment they display in advocating for more research funding reflects the fact that everyday, they live with the consequences of the lack of effective therapies. So as we at CIRM, think about the stem cell agency’s future and are putting together a new Strategic Plan to help shape the direction we take, it only makes sense for us to turn to the patient advocate community for their thoughts and ideas on what that future should look like.
That’s why we are setting up three meetings in the next ten days in San Diego, Los Angeles and San Francisco to give our patient advocates a chance to let us know what they think, in person.
We have already sent our key stakeholders a survey to get their thoughts on the general direction for the Strategic Plan, but there is a big difference between ticking a box and having a conversation. These upcoming meetings are a chance to talk together, to explore ideas and really flesh out the details of what this Strategic Plan could be and should be.
Our President and CEO, Dr. C. Randal Mills wants each of those meetings to be an opportunity to hear, first hand, what people would like to see as we enter our second decade. We have close to one billion dollars left to invest in research so there’s a lot at stake and this is a great chance for patient advocates to help shape our next five years.
Every voice counts, so join us and make sure that yours is heard.
The events are:
San Diego, Monday, July 13th at noon at Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037
Los Angeles: Tuesday, July 14th at noon at Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, 1425 San Pablo Street, 1st floor conf. room Los Angeles, CA 90033
San Francisco: Wednesday, July 15th at noon at CIRM, 210 King Street (3rd floor), San Francisco, CA 94107
There will be parking at each event and a light lunch will be served.
We hope to see you at one of them and if you do plan on coming please RSVP to email@example.com
And of course please feel free to share this invitation to anyone you think might be interested in having their voice heard. We all have a stake in this.
Take a moment to feel your arm and wrist bones. They’re a lot more like solid rock than the soft stretchy skin that covers them. But bone is very much a living tissue continually being broken down and built back up in a process called bone remodeling. In people with osteoporosis, this balance tips toward bone breakdown leading to more porous, fragile bones with increased risk of fractures. An estimated ten million people in the U.S. have osteoporosis accounting for 1.5 million fractures annually at a cost of $17 billion in medical care, not to mention the emotional toll of these often debilitating and even life threatening injuries.
Fluorescent imaging of mouse spines. Treatment with NELL-1 (right) shows greater bone formation compared to untreated mice (left). Credit: Broad Stem Cell Research Center
This week a CIRM-funded research team at UCLA reported in Nature Communications that injection of a human protein called NELL-1 into the blood of mice with osteoporosis-like symptoms tipped the balance back toward bone formation. In a large animal study, delivering NELL-1 directly into the spine also led to increased bone volume. In a university press release, co-senior author Kang Ting spoke of his hopes that these results open up a new therapeutic avenue for treating osteoporosis and other ailments:
“Our end goal is really to harness the bone forming properties of NELL-1 to better treat patients with diverse causes of bone loss, from trauma in military personnel to osteoporosis from age, disease or very weak gravity, which causes bone loss in astronauts.”
In petri dish experiments leading up to these animal results, the research team showed that NELL-1 acts by increasing the specialization of mesenchymal stem cells – a type of adult stem cell found in the bone marrow and fat – into osteoblasts, the cells responsible for building new bone. At the same time, NELL-1 reduced the generation of osteoclasts, the cells responsible for the breakdown, or resorption, of bone. This dual action of NELL-1 explains how it improved the osteoporosis-like symptoms in the animals. Check out this fascinating animation for a visual description of osteoblasts and osteoclasts:
Many of the other molecules that promote bone growth aren’t as efficient as NELL-1: while they increase osteoblast numbers they also increase osteoclasts to some extent. For example, Fosamax is a drug prescribed to women with osteoporosis to help build stronger bones but long-term use has been associated with even more brittle bones and fractures. So this finding with NELL-1 sets it apart and hints at fewer side effects as a therapeutic. Still, it’s known to play a role in brain, cartilage, and blood vessel development so careful studies of non-bone effects are needed as the team pursues a road to the clinic.
For more information about CIRM-funded projects related to osteoporosis, visit our online fact sheet.
And now, we’d like to announce our latest exciting change: we’ve given our website a facelift that reflects the new CIRM 2.0. Allow us to introduce you to the new digital home of California’s Stem Cell Agency:
Our mission—accelerating stem cell treatments to patients with unmet medical needs—informs everything we do here at CIRM, and the redesign of our website is no different. In improving our site, we hope to better serve two important audiences who are critical in us achieving our mission:
Current and potential grantees from research institutions and industry; and
Patients, patient advocates and the public at large who are helping others understand how CIRM-funded scientists are turning stem cells into cures.
We are also using this opportunity to improve the way we are viewed on mobile devices. With up to 40 percent of our visitors coming to cirm.ca.gov via a smartphone or tablet, we wanted to create a superior mobile user experience—so that people can easily access the same content whether they are at home or on the go.
We began this project just a few short months ago, and are thankful for a stellar team of in-house staff and contractors who each dove in to lend a hand. We are especially grateful to Radiant, who worked with CIRM to develop an improved design and navigation.
As part of the process of updating the website we also took the opportunity to update our logo. The old logo was ten years old, an eternity in the age of the Internet. We wanted something that reflected our new streamlined approach to funding, something that was visually appealing and contemporary and something that immediately connected the viewer to who we are and what we do. We hope you like it.
So please, take a look around at the new cirm.ca.gov—we hope you enjoy using it as much as we enjoyed creating it for you. And of course if you have any thoughts or suggestions on how we can improve this even more we’d love to hear from you in the comments below.