New Video: Defeating Sickle Cell Disease with Stem Cells + Gene Therapy

Suffering with an incurable illness is no laughing matter. But last year when we debuted the pilot episode of Stem Cells in Your Face, a lighthearted video series that describes specific diseases and explains the latest progress in stem cell-based therapies, we hoped that a mix of science and humor would help make the information stick in the minds of our viewers. We were thrilled, based on your comments, that you enjoyed watching Treating ALS with a Disease in a Dish as much as we enjoyed producing it and that you wanted to see more:

“Very informative yet easy to understand pilot episode! Hope to see more in this series soon!”

“Might I suggest highlighting a different disease CIRM focuses on in each video?”

Ask and you shall receive. This week we’ve posted the second installment: Defeating Sickle Cell Disease with Stem Cells + Jean Gene Therapy which is being rolled out as a companion piece to our new blog feature series, Genes + Cells.

The video highlights a CIRM-funded clinical trial at UCLA that is testing a stem cell and gene therapy treatment for sickle cell disease. This awful genetic disorder causes red blood cells to assume a sickle shape, clogging blood vessels and producing episodes of excruciating pain, called crises, and leading to progressive organ damage. By twenty years of age about 15 percent of people with sickle cell disease have had major strokes and by 40 almost half of the patients have significant mental dysfunction. The disease strikes one in 500 African Americans and 1 in 36,000 Hispanic people.

A standard treatment for sickle cell disease is a blood transfusion but the benefits are short-lived and require repeated procedures. Bone marrow transplants can be curative but they require a well-matched blood donor which is hard to find and can still be very risky. The UCLA team, on the other hand, aims to correct the sickle cell genetic mutation within the blood stem cells of the patient, which in theory could provide a life-long supply of normal shaped red blood cells. Don Kohn, the lead scientist on the team, explains their strategy in the video:

“The approach that we’re looking at would be to take the patient’s own bone marrow, isolate the [blood] stem cells, in the laboratory put in the gene we’ve been working on that prevents the red blood cells from sickling. So transplanting their own bone marrow back to them in theory should be safe, we don’t have to worry about rejection.“

If all goes well, sickle cell disease may soon be a thing of the past. As patient advocate Adrienne Shapiro has so eloquently stated in a previous Stories of Hope blog post:

“It’s my true belief that I’m going to be the last woman in my family to have a child with sickle cell disease. My afflicted daughter is going to be the last child to suffer, and my other daughter [who does not have the disease but carries the sickle cell mutation] is going to be the last one to fear [passing on the disease to her children]. Stem cells are going to fix this for us and many other families.”

This clinical trial represents one of the first trials to be part of CIRM’s Alpha Stem Cell Network. To learn more, visit our Alpha Clinic webpage. And for more details about CIRM-funding of sickle cell disease research visit these pages:

Clearing up chemobrain: cancer therapy-induced memory problems reversed by stem cells

You’d think receiving a cancer diagnosis and then suffering through chemo and/or radiation therapy would be traumatic enough. But as many as 75% of cancer survivors are afflicted by memory and attention problems long after their cancer therapy.

This condition, often called “chemobrain”, shouldn’t be misunderstood as being confined to cancers of the brain. A 2012 analysis of nearly 200 women who had been treated with chemotherapy for breast cancer showed they had ongoing memory and information processing deficits that persisted more than twenty years after their last round of treatment. And young cancer survivors are particularly vulnerable to reduced IQs, nonsocial behavior and an extremely lowered quality of life.

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CIRM grantee and UC Irvine professor Charles Limoli, PhD is senior author of this study

Chemotherapy drugs work by killing off cells that are dividing rapidly, a hallmark of cancer cells. But this brute force method also kills other rapidly dividing cells that are critical for normal bodily functions. In the case of chemobrain, it’s thought that damage to newly formed brain cells in the hippocampus, the memory center of the brain, is the culprit. A UC Irvine study published this week in Cancer Research supports that idea in experiments that test the effect of transplanting human nerve stem cells in rats. The research team leader Charles Limoli, a CIRM grantee and UC Irvine professor of radiation oncology, summarized the groundbreaking results in a press release (note: this study is not funded by CIRM):

“Our findings provide the first solid evidence that transplantation of human neural stem cells can be used to reverse chemotherapeutic-induced damage of healthy tissue in the brain.”

The novel place recognition test is evaluate memory function. Animal is initially presented with identical objects (red circles). Then a new object is introduced (blue square). A healthy mouse will investigate the blue square.

The novel place recognition test, one of several tests used in this study to evaluate memory function.  During training setup (left), the rodent is familiarized with identical objects (red circles). Later, rodent returns now in presence of a new object (blue square). A healthy mouse will investigate the new object during testing setup (right). Image credit: KnowingNeurons.com

So how the heck do you observe chemotherapy-induced cognitive problems in a rodent let alone show that stem cells can rescue the damage? In the study, the rats undergo a variety of recognition memory tasks after a typical chemotherapy drug treatment. For instance, in the novel place recognition test, an animal is familiarized with two identical objects inside a test “arena”. Later, the animal is returned to the arena but a new object is swapped in for one of the previous objects. Rats given chemotherapy treatment but no stem cell surgery (they’re implanted with a saline solution instead) do not show a preference for the novel object. But rats given chemotherapy and the human nerve stem cell surgery prefer the novel object. This novel seeking behavior is also seen in control rats given no chemotherapy. So these results demonstrate that the transplanted stem cells rescued normal memory recognition in the chemotherapy-treated rats.

The research team also saw differences within the brains of these groups of rats that match up with these behavioral results. First, they confirmed that the transplanted human stem cells had indeed survived and grafted into the rat brains and had matured into the correct type of brain cells. Next they looked at chemotherapy-induced inflammation of brain tissue. The brains of chemotherapy-treated rats with no stem cell transplantation showed increased number of active immune cells compared to the control and stem cell transplanted animals. In another experiment, a detailed analysis of the structure of individual nerve cells showed extensive damage in the chemotherapy treated rats compared to controls. Again, this damage was reversed in chemotherapy treated rats that also received the stem cell transplant.

Rat nerve cells (black structures) in memory center of the brain are damaged by chemotherapy (left); transplanting human nerve stem cells reverses the damage (right)

Rat nerve cells (black structures) in memory center of the brain are damaged by chemotherapy (left); transplanting human nerve stem cells reverses the damage (right). Image credit: Acharya et al. Cancer Research 75(4) p. 676

As many researchers can tell you, these exciting results in animals don’t guarantee a human therapy is around the corner. But still, says Limoli:

“This research suggests that stem cell therapies may one day be implemented in the clinic to provide relief to patients suffering from cognitive impairments incurred as a result of their cancer treatments. While much work remains, a clinical trial analyzing the safety of such approaches may be possible within a few years.”

For a more details about the role of stem cells in chemobrain, watch this recent presentation to the CIRM Governing Board by CIRM grantee and Stanford professor Michelle Monje.

Money matters: how investing in research advances stem cell science

Our goal at the stem cell agency is simple; to accelerate the development of successful therapies to patients with unmet medical needs. But on the way to doing that something interesting is happening; we’re helping advance the scientific understanding of stem cells and building a robust stem cell research community in California in the process.

You don’t have to take our word for it. A new paper in the journal Cell Stem Cell takes a look at the impact that state funding for stem cell research has had on scientific publications. The question the researchers posed was; have the states that fund stem cell research seen an increase in their share of scientific publications in the field? The answer, at least in California’s case, is absolutely yes.

Let’s back up a little. In the late 1990’s and early 2000’s the field of stem cell research was considered quite controversial, particularly when it came to human embryonic stem cells (hESCs). To help scientists get around some of the restrictions that were placed on the use of federal funds to do hESC research a number of states voted to provide their own funding for this work. This research focuses on four of the biggest supporters of this work: California, Connecticut, Maryland, and New York.

The researchers looked at the following factors:

  1. The percentage of scientific publications in the U.S.
  2. With at least one author from those four states.
  3. That focused on hESCs and induced pluripotent stem cells (iPSCs).
  4. Comparing the numbers from before the state funding kicked in to after.

Finally – stay with me here, we’re almost done – they compared those numbers to the number of publications for two other areas of non-controversial biomedical research, RNAi and cancer. For California the results were clear. The percentage of papers on RNAi and cancer from 1996 – 2013, that had at least one California author, stayed fairly consistent (between 15-18%). However, the percentage of papers on hESCs and iPSCS with a California author rose from zero in 1998 and 2006 (the year each was discovered) to a high of 45 percent in 2009. That has since dropped down a little but still remains consistently high.

Study graphic study code The article says the reason for this is really rather obvious: “that state funding programs appear to have contributed to over-performance in the field.”

“After the California Institute for Regenerative Medicine (CIRM) issued its first grants in April 2006, the share of articles acknowledging California funding increased rapidly. Between 2010 and 2013, approximately 55% of hESC-related articles published with at least one California author acknowledged state funding, suggesting that this funding program played an important role as California maintained and built upon its early leadership in the field.”

Connecticut also saw its share of publications rise, though not as dramatically as California. Maryland and New York, in contrast, saw their share of publications remain consistent. However, as the researchers point out, with California gobbling up so much more of the available space in these journals, the fact that both states kept their share consistent was an achievement in itself.

The researchers acknowledge that scientific publications are “only one measure of the impact of state science programs” and say it’s important we look at other measures as well – such as how many clinical trials arise from that research. Nonetheless they conclude by saying:

“This analysis illustrating the relative performance of states in the production of stem-cell-related research publications provides a useful starting point for policymakers and, potentially, voters considering the future of state stem cell funding efforts as well as others interested in state science and technology policy more generally.”

Stem Cell Stories that Caught Your Eye: The Most Popular Stem Cellar Stories of 2014

2014 marked an extraordinary year for regenerative medicine and for CIRM. We welcomed a new president, several of our research programs have moved into clinical trials—and our goal of accelerating treatments for patients in need is within our grasp.

As we look back we’d like to revisit The Stem Cellar’s ten most popular stories of 2014. We hope you enjoyed reading them as much as we did reporting them. And from all of us here at the Stem Cell Agency we wish you a Happy Holidays and New Year.

10. UCSD Team Launches CIRM-Funded Trial to Test Safety of New Leukemia Drug

9. Creating a Genetic Model for Autism, with a Little Help from the Tooth Fairy

8. A Tumor’s Trojan Horse: CIRM Researchers Build Nanoparticles to Infiltrate Hard-to-Reach Tumors

7. CIRM funded therapy for type 1 diabetes gets FDA approval for clinical trial

6. New Videos: Living with Crohn’s Disease and Working Towards a Stem Cell Therapy

5. Creativity Program Students Reach New Heights with Stem Cell-Themed Rendition of “Let it Go”

4. Scientists Reach Yet Another Milestone towards Treating Type 1 Diabetes

3. Meet the Stem Cell Agency President C. Randal Mills

2. Truth or Consequences: how to spot a liar and what to do once you catch them

1. UCLA team cures infants of often-fatal “bubble baby” disease by inserting gene in their stem cells; sickle cell disease is next target

CIRM-Funded UC-Irvine Team Set to Launch Stem Cell Trial for Retinitis Pigmentosa in 2015

Rosalinda Barrero has often been mistaken for a rude snob. She has the habit of not saying hello or even acknowledging the presence of acquaintances that she passes around town. But in fact this kind, loving mom of three has been steadily losing her vision over a lifetime. And she doesn’t seem blind because people are still vaguely visible as shadowy ghosts but their faces are unrecognizable.

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Rosalinda Barrero is legally blind due to retinitis pigmentosa. She eagerly awaits the launch of a CIRM-funded trial that will test a candidate stem cell-based treatment.

Barrero is stricken with retinitis pigmentosa (RP) an incurable genetic disease that gradually destroys the light sensing nerve cells, called photoreceptors, located in the retina at the back of the eye. In October, Rosalinda and her husband German spoke to the CIRM governing Board about the devastating impact of RP on their lives and their excitement about a soon to begin CIRM-funded stem cell-based clinical trial for the treatment of RP. The project is headed by UC-Irvine associate professor Henry Klassen, MD, PhD, who also spoke to the Board. Videos of their presentations are now available on our website and below:

Over 3000 known genetic mutations can give rise to RP. These mutations lead to the gradual deterioration of the so-called rod photoreceptors. These rod cells specifically provide our night vision — like on a moonless night. Rosalinda clearly remembers her childhood struggles with night blindness on Halloween:

“I didn’t like trick-or-treating because I couldn’t see in the dark. I ‘d say ‘this is not fun! I’m tripping! I’m losing all my candy!’ I wanted to stay home and hand out candy”

Unfortunately the disease doesn’t stop there. As the rods continue to die off another type of photoreceptor, the cone cells, become innocent bystanders and also gradually deteriorate later in life. As Dr. Klassen explained, it’s the cone cells that are critical for our sight:

“The cones are what humans use for almost all of their vision. Even at night when you’re driving a car with headlights you’re using mainly your cones. So if we could preserve the cones we can really help the patient.”

With the support of a $17 million CIRM Disease Team grant, Klassen and his team anticipates starting a stem-call based clinical trial in early 2015 with the ultimate aim of healing those cone cells in RP patients. The therapy uses a type of immature stem cell of the retina called retinal progenitor cells. The proposed approach relies on the injection of the cells into the jelly of the eye near the retina to promote indirect healing. Klassen explained the project rationale to the Board:

“So we’re talking about little clusters of cells that could fit on the head of a pin in the jelly of the eye and they’re just floating there. And what are they going to do? Well they just sit there and secrete all the factors they normally secrete during retinal development and diffuse into the retina. Once in the retina we believe [based on animal studies] those factors are going to reprogram the photoreceptors into becoming functional again instead of going down that road where they’re going to commit suicide.”

Rosalinda is beyond thrilled with the prospect of being a recipient of this candidate therapy. Her husband German echoed her hopefulness to the Board:

“Even though it’s not a deadly disease, [the therapy] would be life-changing not only for Rosie it would be for everyone around her. “

To learn more about CIRM-funded research related to blindness, visit our fact sheet.

UCLA team cures infants of often-fatal “bubble baby” disease by inserting gene in their stem cells; sickle cell disease is next target

Poopy diapers, ear-splitting cries, and sleepless nights: sure, the first few weeks of parenthood are grueling but those other moments of cuddling and kissing your little baby are pure bliss.

The bubble boy.  Born in 1971 with SCID, David Vetter lived in a sterile bubble to avoid outside germs that could kill him. He died in 1984 at 12 due to complications from a bone marrow transplant. [Credit: Baylor College of Medicine Archives]

The bubble boy. Born in 1971 with SCID, David Vetter lived in a sterile bubble to avoid outside germs that could kill him. He died in 1984 at 12 due to complications from a bone marrow transplant. [Credit: Baylor College of Medicine Archives]

That wasn’t the case for Alysia and Christian Padilla-Vacarro of Corona, California. Close contact with their infant daughter Evangelina, born in 2012, was off limits. She was diagnosed with a genetic disease that left her with no immune system and no ability to fight off infections so even a minor cold could kill her.

Evangelina was born with Severe Combined Immunodeficiency (SCID) also called “bubble baby” disease, a term coined in the 1970s when the only way to manage the disease was isolating the child in a super clean environment to avoid exposure to germs. Bone marrow transplants from a matched sibling offer a cure but many kids don’t have a match, which makes a transplant very risky. Sadly, many SCID infants die within the first year of life.

Until now, that is.

Today, a UCLA research team led by Donald Kohn, M.D., announced a stunning breakthrough cure that saved Evangelina’s life and all 18 children who have so far participated in the clinical trial. Kohn—the director of UCLA’s Human Gene Medicine Program—described the treatment strategy in a video interview with CIRM (watch the video below):

“We collect some of the baby’s own bone marrow, isolate the [blood] stem cells, add the gene that they’re missing that their immune system needs and then transplant the cells back to them. “

Inserting the missing gene, called ADA, into the blood stem cells restores the cells’ ability to produce a healthy immune system. And since the cells originally came from the infant, there’s no worry about the possible life-threatening complications from receiving non-matched donor cells.

This breakthrough didn’t occur overnight. Kohn and colleagues have been plugging away for over twenty years carrying out trials, observing their limitations and going back to lab to improve the technology. Their dedication has paid off. As Kohn states in a press release:

“All of the children with SCID that I have treated in these stem cell clinical trials would have died in a year or less without this gene therapy, instead they are all thriving with fully functioning immune systems.”

Alysia Padilla-Vacarro and daughter Evangelina on the day of her gene therapy treatment. Evangelina, now two years old, has had her immune system restored and lives a healthy and normal life. [Credit: UCLA Broad Center of Regenerative Medicine and Stem Cell Research.]

Alysia Padilla-Vacarro and daughter Evangelina on the day of her gene therapy treatment. Evangelina, now two years old, has had her immune system restored and lives a healthy and normal life. [Credit: UCLA Broad Center of Regenerative Medicine and Stem Cell Research.]

For the Padilla-Vacarro family, the dark days after Evangelina’s grave diagnosis have given way to a bright future. Alysia, Evangelina’s mom, poignantly recalled her daughter’s initial recovery:

”It was only around six weeks after the procedure when Dr. Kohn told us Evangelina can finally be taken outside. To finally kiss your child on the lips, to hold her, it’s impossible to describe what a gift that is. I gave birth to my daughter, but Dr. Kohn gave my baby life.”

The team’s next step is to get approval by the Food and Drug Administration (FDA) to provide this treatment to all SCID infants missing the ADA gene.

At the same time, Kohn and colleagues are adapting this treatment approach to cure sickle cell disease, a genetic disease that leads to sickle shaped red blood cells. These misshapen cells are prone to clumping causing debilitating pain, risk of stroke, organ damage and a shortened life span. CIRM is providing over $13 million in funding to support the UCLA team’s clinical trial set to start early next year.

For more information about CIRM-funded sickle cell disease research, visit our fact sheet.

Spinal cord injury and stem cell research; find out the latest in a Google Hangout

Spinal cord injuries are devastating, leaving the person injured facing a life time of challenges, and placing a huge strain on their family and loved ones who help care for them.

The numbers affected are not small. More than a quarter of a million Americans are living with spinal cord injuries and there are more than 11,000 new cases each year.

It’s not just a devastating injury, it’s also an expensive one. According to the National Spinal Cord Injury Statistical Center it can cost more than $775,000 to care for a patient in the first year after injury, and the estimated lifetime costs due to spinal cord injury can be as high as $3 million.

Right now there is no cure, and treatment options are very limited. We have heard for several years now about stem cell research aimed at helping people with spinal cord injuries, but where is that research and how close are we to testing the most promising approaches in people?

That’s going to be the focus of a Google Hangout on Spinal Cord Injury and Stem Cell Research that we are hosting tomorrow, Tuesday, November 18 from noon till 1pm PST.

We’ll be looking at the latest stem cell-based treatments for spinal cord injury including work being done by Asterias Biotherapeutics, which was recently given approval by the Food and Drug Administration (FDA) to start a clinical trial for spinal cord injury. We are giving Asterias $14.3 million to carry out that trial and you can read more about that work here.

We’re fortunate in having three great guests for the Hangout: Jane Lebkowski, Ph.D., the President of research and development at Asterias; Roman Reed, a patient advocate and tireless champion of stem cell research and the founder of the Roman Reed Foundation; and Kevin Whittlesey, Ph.D., a CIRM science officer, who will discuss other CIRM-funded research that aims to better understand spinal cord injury and to bring stem cell-based therapies to clinic trials.

You can find out how to join the Hangout by clicking on the event page link: http://bit.ly/1sh1Dsm

The event is free and interactive, so you’ll be able to ask questions of our experts. You don’t need a Google+ account to watch the Hangout – just visit the event page at the specified time. If you do have a G+ account, please RSVP at the event page (link shown above). Also, with the G+ account you can ask questions in the comment box on this event page. Otherwise, you can tweet questions using #AskCIRMSCI or email us at info@cirm.ca.gov.

We look forward to seeing you there!

New Videos: Living with Crohn’s Disease and Working Towards a Stem Cell Therapy

Note: the two videos below are also available on our website

She doesn’t want your sympathy. She doesn’t want your admiration. She just wants your understanding.

Rachel Bonner, a sixteen-year-old high school student and founder of the Hope for Crohn’s charity, spoke to the CIRM governing Board on September 10th about what it’s like living with Crohn’s disease. In the eight years since her diagnosis, Rachel has come a long way in talking publicly about her condition:

“I never thought I’d stand up here and admit to wearing a diaper while being in middle school. But Crohn’s turns from a secret struggle to something I want to share with other people. And ultimately have others understand the life of a Crohn’s patient just a bit more. “

Crohn’s disease is a type of inflammatory bowel disease (IBD) in which the intestines are chronically inflamed. Symptoms of Crohn’s include a frequent need to pass bowel movements, constant diarrhea, rectal bleeding, fatigue and loss of appetite.

In a healthy individual, the friendly bacteria living in the gut are ignored by the immune system. But in the case of IBD, the immune cells attack these bacteria as foreign invaders, causing an inflammatory response. The sustained inflammation eventually damages the gut wall causing the symptoms of IBD.

Current therapies for IBD focus solely on treating the inflammation. Dr. Ophir Klein, a CIRM grantee and UCSF researcher, also spoke to the governing Board and described another treatment avenue:

“There’s another component that’s been under-explored and potentially has a lot of impact therapeutically which is the regenerative aspects of the condition because after the inflammation occurs in the gut, the gut needs to heal, and that healing comes from stem cells. “

In his presentation to the Board, Dr. Klein detailed his lab’s work to understand how stem cells regulate the healing of the intestine and to eventually find cures for IBD.

Although Rachel and her doctors have found a treatment sweet spot, which has kept her Crohn’s at bay, she still holds out hope that a cure, perhaps from a stem-cell based therapy, is not too far away:

“Everyday I go to sleep hoping that this treatment sweet spot will work until they find a cure”

Disease in a Dish – That’s a Mouthful: Using Human Stem Cells to Find ALS Treatments

Saying “let’s put some shrimp on the barbie” will whet an Australian’s appetite for barbequed prawns but for an American it conjures up an odd image of placing shrimp on a Barbie doll. This sort of word play confusion doesn’t just happen across continents but also between scientists and the public.

Take “disease in a dish” for example. To a stem cell scientist, this phrase right away describes a powerful way to study human disease in the lab using a Nobel Prize winning technique called induced pluripotent stem cells (iPSC). But to a non-scientist it sounds like a scene from some disgusting sci-fi horror cooking show.

Our latest video Disease in a Dish: That’s a Mouthful takes a lighthearted approach to help clear up any head scratching over this phrase. Although it’s injected with humor, the video focuses on a dreadful disease: amyotrophic lateral sclerosis (ALS). Also known as Lou Gehrig’s disease, it’s a disorder in which nerve cells that control muscle movement die. There are no effective treatments and it’s always fatal, usually within 3 to 5 years after diagnosis.

To explain disease in a dish, the video summarizes a Science Translation Medicine publication of CIRM-funded research reported by the laboratory of Robert Baloh, M.D., Ph.D., director of Cedars-Sinai’s multidisciplinary ALS Program. In the study, skin cells from patients with an inherited form of ALS were used to create nerve cells in a petri dish that exhibit the same genetic defects found in the neurons of ALS patients. With this disease in a dish, the team identified a possible cause of the disease: the cells overproduce molecules causing a toxic buildup that affects neuron function. The researchers devised a way to block the toxic buildup, which may point to a new therapeutic strategy.

In a press release, Clive Svendsen, Ph.D., a co-author on the publication and director of the Cedars-Sinai Regenerative Medicine Institute had this perspective on the results:

“ALS may be the cruelest, most severe neurological disease, but I believe the stem cell approach used in this collaborative effort holds the key to unlocking the mysteries of this and other devastating disorders.”

The video is the pilot episode of Stem Cells in Your Face, which we hope will be an ongoing informational series that helps explain the latest advances toward stem cell-based therapies.

For more information about CIRM-funded ALS research, visit our ALS fact sheet.