Video: Reversing autism in the lab with help from stem cells and the tooth fairy


I look at my son a lot and feel like he’s trapped inside his own brain. Circuits are going crazy. He can’t figure it out. Of course, I can’t figure it out. And I think he deserves to have a voice…He’s never said I love you. He’s never said “Mom” with any meaning…I feel like he has been stolen from me.

Those sobering words from Jen, mother of 10 year-old Milo who has a severe form of autism, were shared during the Spotlight on Autism seminar at the March 13th CIRM governing Board meeting. You can watch a video of the Spotlight on our website (a short version with just Jen’s video clip is also available). CIRM grantee Dr. Alysson Muotri, the featured speaker who studies autism at UC-San Diego, explained that

people with autism have difficulty with language and social interaction and often get stuck in repetitive, focused behavior. It’s a spectrum, which means there are patients that are less severe and patients that are more severe…the CDC [Centers for Disease Control] estimates that we have 1% of the population with autism. If you are a boy, or male, you have a higher chance to be diagnosed.

Being such a complex, wide-ranging and very human behavioral disorder, how can researchers possibly learn the cause let alone develop treatments for autism? With the help of the tooth fairy, yes the tooth fairy, and stem cells, Dr. Muotri presented some startling research results that open a window into one day treating autism.

Dr. Muotri set out to compare the differences between the brain cells of autistic versus unaffected individuals. Since brain biopsies would be much too risky, impractical, and possibly unethical, he relied on the induced pluripotent stem cell (iPS) technique in which a cell sample from an accessible part of the body is grown in a petri dish, reprogrammed back into an embryonic stem cell-like state, and then transformed into brain cells.

To collect cell samples efficiently and non-invasively, Muotri devised a Fairy Tooth Kit Collection social media campaign in which autistic and unaffected kids could donate their baby teeth when they fall out. Muotri’s team then extracted the dental pulp cells from the teeth to ultimately generate iPS-derived neurons, the cells that send information throughout the brain and the body via electrical signals.

An initial glance between the autistic and unaffected neurons showed no differences. But on closer inspection the autistic neurons had fewer structures that are key to making connections with other neurons. But Muotri found after trial and error, that a particular molecule could restore the lost connections and lowered brain activity in the autistic neurons.

He also found that simply growing the autistic cells with other types of brain cells from unaffected individuals could also reverse the autistic characteristics. I encourage you to watch the video for more details of these fascinating results.

Does this mean we have a cure for autism? Not quite. But this human “model” of autism gives Muotri and other researchers a solid experimental platform for delving further into the changes that occur in the wide spectrum of autistic brain cells. And it helps them to understand more precisely how certain drugs or cellular environments reverse the autism in a petri dish. These studies are critical for one day propelling the work toward testing treatments in people.

And you can thank Dr. Muotri, his team, and the tooth fairy for that.

Read a blog, press release and brochure to learn about CIRM’s initiative to collect thousands of tissue samples in order to create and bank iPS cells from people with a wide range of disorders including autism. Also for more information about CIRM-funded autism research, visit our autism fact sheet page.

Todd Dubnicoff

Stem cells helping unlock some of the mysteries of bipolar disorder

One of the reasons cancer experts have been able to make big advances in recent years is because they can take a tumor and biopsy it and understand its makeup. With bipolar disorder – and indeed with any brain condition – we haven’t been able to do that because it’s considered bad form to biopsy a brain while someone is still using it.

But now, thanks to stem cells, and in particular thanks to the ones known as induced pluripotent stem (iPS) cells we can do just that; examine how a disease like bipolar disorder impacts the cells in the brain.

Part of the problem with treating bipolar disorder is that we don’t really know what causes it. But in a study published in the journal Translational Psychiatry, researchers at the University of Michigan demonstrated a way to compare the neurons, or brain nerve cells, of people with the condition to those of people without.

They took skin samples from people with bipolar disorder and then turned, or reprogrammed, them into becoming iPS cells, which have the ability to become any other cell in the body. They then turned those iPS cells into neurons that showed differences in how they communicate amongst themselves compared to normal neurons.

In a news release accompanying the article, study co-leader Sue O’Brien talked about the significance of creating these new brain cells:

“This gives us a model that we can use to examine how cells behave as they develop into neurons. Already, we see that cells from people with bipolar disorder are different in how often they express certain genes, how they differentiate into neurons, how they communicate, and how they respond to lithium.”

The researchers hope this work will help them understand why bipolar disorder runs in families, even when no single gene appears to be the cause. The other hope, of course, is that this work will ultimately lead to new and improved treatments for the condition.

While we played no role in this study we are using a similar approach with our iPSC Bank Initiative, where we are taking blood or skin samples from thousands of individuals and turning them into stem cells. Because those cells will come from people with diseases like Alzheimer’s, heart disease and vision loss – as well as a variety of neurological conditions such as autism – they will enable us to create real-life models to study the diseases and to help us develop a deeper understanding of these conditions and hopefully lead to more effective treatments.

Koala bears and cancer cells – how our Hangout had good news in the fight against leukemia


What does a Koala bear have to do with finding more effective treatments for leukemia? Well, Dr. Catriona Jamieson says the connection is really quite simple and she explained it in our Google Hangout on Leukemia yesterday. It’s quite a fun story.

Dr. Jamieson is the Director of Stem Cell Research at the Moore Cancer Center at the University of California San Diego and a number of her research projects are already in clinical trials in patients. She talked about the results they’ve seen so far, and their hopes for the future.

We were also fortunate to have Dr. Ravi Majeti of Stanford University. Dr. Majeti and his team are working on a new approach that targets cancerous stem cells in acute myeloid leukemia and is hopefully going to be in clinical trials later this year.

Those two scientists represent the most advanced stage of the research we are funding. Dr. Karen Berry – a Science Officer here at the stem cell agency – walked us through some of the other really exciting work we are supporting that is at an earlier stages of development.

 Between the three of them they painted an optimistic look at the state of stem cell research into leukemia, the progress we are making, and the obstacles we still have to overcome.

You can watch the full California stem cell agency Google Hangout on Leukemia on our YouTube Channel. And of course feel free to share this link with anyone you think might be interested.

kevin mccormack

iPS type stem cells pushed to become replacement tissue for bladder repair, possibly after cancer

A CIRM-funded team at the University of California at Davis has developed an efficient method for coaxing early-stage stem cells known as pluripotent cells into becoming the specialized tissue that lines our bladders and protects them from the acid in urine.

Because the bladder is one of our simpler organs it has been one of the early success stories of using tissue engineering to replace an organ. Teams have removed a few semi-specialized cells from patients’ bladders, encouraged them to proliferate in the lab and then seeded them on artificial scaffolds that can become patches or in some cases whole new organs. But this only works when you can harvest healthy versions of these precursor, or progenitor cells. That can be done in children born with bladder defects and in some patients with damage due to disease, but it cannot be done in patients with damage due to bladder cancer. And those patients make up 90 percent of people needing bladder repair.

That led Eric Kurzrock and the other members of his Davis team to work with pluripotent stem cells, first embryonic stem cells (ESCs) and then iPS cells generated by reprogramming skin or other adult tissue. They developed a procedure that did not require genetic manipulation to drive the stem cells to become bladder cells and a method to keep those cells growing in the lab for a long time, something that is key to bioengineering a larger patch or whole organ.

The team published its work in the journal CIRM-helped to found, Stem Cells Translational Medicine, and the San Francisco Chronicles’ web site SFGate ran the publisher’s press release. The release had a quote from Jan Nolte, one of the study authors who directs the CIRM-funded regenerative medicine center at Davis. She talks about the broader implications of being able to direct a patient’s own cells to become iPS cells and then to direct those to become repair tissue:

“What’s exciting about this discovery is that it also opens up an array of opportunities using pluripotent cells. When we can reliably direct and differentiate pluripotent stem cells, we have more options to develop new and effective regenerative medicine therapies. The protocols we used to create bladder tissue also provide insight into other types of tissue regeneration.”

Researchers are pursuing many different avenues to developing replacement tissues and organs. You can read about many of those approaches in the CIRM tissue engineering workshop report.

Don Gibbons

CIRM funding: Eric Kurzrock RB2-01567

Progress you can see – how CIRM-funded projects are heading to clinical trials

Progress in science can take time, and it can seem like a really long slog when so many people are looking to you for breakthroughs that could save their life or the life of someone they love. But progress is being made in stem cell research with a growing number of promising therapies moving out of the lab and into clinical trials in people.

For proof of that here is one slide from a presentation that Dr. Ellen Feigal, our Senior Vice President for Research and Development, made at our March Board meeting. It shows how the Disease Teams we are funding are moving rapidly towards clinical trials. In fact of the first 14 Disease Teams we funded, nine have successfully progressed to the point where they are either already enrolling patients for clinical trials or expect to be enrolling patients by the end of this year, and they just began the CIRM part of their projects in 2010.

The upward slope of the graph above shows how each year more and more of the projects we fund are meeting the targets we have set for them with an ultimate goal of reaching a clinical trial. One of the major milestones in reaching clinical trials is filing the so-called Investigational New Drug (IND) application to the Food and Drug Administration (FDA). This is such an important step that research teams frequently organize “pre-IND” meetings with the FDA to make sure that all their ducks are in a row. Acceptance of the IND is a green light to begin testing the stem cell-based therapy in people.

As you can see from the chart, the IND meetings, filings, and approvals have steadily increased since we begun our Disease Team programs several years ago.

Two trials are already underway, for HIV/AIDS and congestive heart failure (helping patients who have had a heart attack) and other trials are expected to begin this year in:
• Cancer – leukemia and solid tumor cancers (such as breast and ovarian)
• Degenerative eye disease
• Type 1 diabetes
• Sickle Cell disease
• Beta-thalassemia – a serious and potentially deadly blood disorder

This is an impressive rate of success. Of course this is only the first step towards approval by the FDA and there are many challenges facing all of these therapies, but to get this many projects to this point in such a relatively short time is no small achievement.

It’s unlikely that all of these will ultimately work out, but we’re confident some will. And we have many more on the way.

If you would like to see more of Dr. Feigal’s presentation on the progress we are making, with a lot more detail on what these individual projects are and the impact they could have on California and the U.S., you can find it on our website.

kevin mccormack

Stem cell stories that caught our eye: iPS cells from drop of blood, leukemia and stem cell backer Jim Stowers

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cells from a drop of blood. One reason Shinya Yamanaka won the Nobel Prize in 2012 was his discovery of iPS type stem cells had the potential to create replacement tissue that matched the patients. But reprogramming adult cells from every patient to be stem cells would be very expensive and time consuming—maybe too time consuming for acutely ill patients. So, many groups have proposed banks of iPS cells from diverse populations so that most people could get donor cells quickly that were closely matched immunologically. CIRM President Alan Trounson is working with an international group to start one such stem cell bank initiative that we wrote about last year.

But, collecting adult tissue from all the diverse populations of the world is problematic. Although the early method of taking skin biopsies to collect adult cells can now be replaced by blood draws, that is still not an optimal solution. So, a team in Singapore has developed a technique that allows the creation of iPS cells from a drop of blood from a simple finger stick, not the tablespoon or more that is currently required. They even devised a system that allows the donors to store and ship the sample themselves. Other researchers will need to verify the efficiency of the new procedure and the quality of the stem cells it creates, but the technique could make a world-wide tissue bank much more feasible.

Stem Cells Translational Medicine, the journal CIRM helped to found, published the study and the web site benzinga picked up the publisher’s press release.

The triumph of keeping leukemia alive in a dish. As resilient as leukemia stem cells can be in patients, you would think it would be easy to culture them in the lab. But that has not been the case. They lose their “stemness” when cultured, which has made it difficult for researchers to find the method to their cancer-causing madness. A team at the University of Montreal has isolated two chemicals that preserve the character of leukemia stem cells in lab culture. This should allow researcher to better understand what regulates their survival and growth and develop drugs to target their vulnerabilities. Nature Methods published the work and Fierce Biotech Research wrote about it.

CIRM funds several projects targeting these treacherous cells including two that hope to begin clinical trials this year. You can read about those projects on our leukemia fact sheet.

Mourning a stem cell champion. Jim Stowers was a hero to friends of mine who work at Washington University in St. Louis. Without him, embryonic stem cell research would probably be illegal in Missouri. He and his wife bankrolled the campaign to fight an effort to criminalize the work in 2006. They had earlier proven their commitment to biomedical research when they created the Stowers Institute in Kansas City in 2000 with a $2 billion endowment. In an obituary in the St. Louis Post-Dispatch William Danforth, chancellor emeritus at Wash U, said Stowers was committed to making the world a better place. We salute him and his efforts.

Don Gibbons

Do you have questions about how stem cells could help people with leukemia? We have answers

Put this day and time in your diary. Tuesday, March 25 from noon till 1pm PT. That’s when we’ll be holding our next Google Hangout and the topic this time is leukemia.

We’ll be bringing together three great scientists to talk about their work and experience in finding cures or more effective therapies for leukemia, when we might see those therapies being tested in patients, and what their thoughts are on future directions for research.

Those experts include:
Dr. Catriona Jamieson, University of California San Diego: Dr. Jamieson’s work focuses on mutant stem cells that can evade chemotherapy and ultimately lead to diseases like leukemia recurring. Her goal is to develop treatments that target those mutant or cancer stem cells, and to develop more selective, less toxic therapies, ones that are easier on patients and harder on the cancer. One potential therapy from her work is already in clinical trials in patients and another is expected to begin clinical trials later this year
Dr. Ravi Majeti, Stanford University: Dr. Majeti is part of a team that has identified a protein that sits on the surface of some cancer cells – including Acute Myeloid Leukemia (AML) – that attaches what he calls a “don’t eat me” sign on the cell so that the body’s own immune defense system doesn’t destroy the cancer, and instead allows it to spread. They have developed an approach that strips that “don’t eat me” sign off the cancer cells, leaving them defenseless and allowing the immune system to destroy them
Dr. Karen Berry, stem cell agency Science Officer: Dr. Berry oversees many of the leukemia research projects that we fund and has a broad base of knowledge about this area.

One thing those brief bios don’t tell you is that these are three incredibly passionate and articulate scientists who enjoy talking about their work and explaining it to the public.

And there’s a lot to talk about. We are making great progress in this area so it promises to be an engaging and encouraging hour.

Google Hangouts are great because not only do they allow you to see and listen to the experts, but you can also ask questions in real time. If you have a Google+ account, you can post questions directly to the Hangout’s event page. You can also Tweet your questions using #AskCIRMLeukemia or email them to Info@CIRM.ca.gov.

Don’t forget: you don’t need a Google+ account to watch, just go to the event page.

And best of all, it’s free.

kevin mccormack

Stem cell society webcast looks at what patients should expect from clinics offering cell therapies

Geoff Lomax is CIRM’s Senior Officer for Medical & Ethical Standards

Yesterday, the International Society for Stem Cell Research (ISSCR) sponsored a public webcast titled: Oversight of Stem Cell Treatments. The Webcast used the example of a recent US District Court of Appeals decision to frame a conversation about the appropriate regulation of stem cell therapies. CIRM grantee Lawrence Goldstein of the University of California at San Diego and Margaret Foster Riley of the University of Virginia School of Law discussed the importance of an effective environment for developing stem cell therapies.

With regard to cell-based therapies, Dr. Goldstein alluded to what he called the “colorless liquid problem.” He was referring to the fact that there are many clinics offering stem cell treatments, but it is often difficult for him, or anyone else, to understand what they are offering.

To address this problem, Dr. Goldstein indicated that any such treatment should include:

· A precise description of the cell treatment and how it will be given to the patient

· A mechanism for experts to review the treatment procedure

· A system for collecting data on the performance of the treatment so we can measure how it does over time and with different patients

· Methods for allowing access to data to “contribute to shared knowledge”

· Accountability mechanisms so there is accountability for various claims about the safety and performance of procedures

Dr. Goldstein and Professor Riley emphasized that “good regulation,” such as that carried out by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), brings these attributes to a system that is flexible and responsive. They emphasized that regulatory bodies are experienced in reviewing information about new treatments for patients, and are committed to getting the best treatments to patients, but they also have an obligation to protect the patients and the public and that means carefully reviewing that information. Members of the public can login to the ISSCR Connect platform to view the archived webcast.

What was interesting about the Webcast is the fact that much of what Dr. Goldstein and Professor Riley emphasized has been incorporated into CIRM’s Alpha Stem Cells Clinic initiative. This program is designed to provide an optimal environment for the development and testing of new cell therapies. The goal is to bring treatments to patients as quickly as possible while ensuring effective safety systems are built into the process. It is great to see CIRM and ISSCR are on the same page.

Geoff Lomax

Is there a doctor in the House? How about a stem cell scientist?

Dr. Raja Kittappa, stem cell researcher and candidate for Congress

Of the 541 members of Congress there are plenty of lawyers (173 in the House and Senate) lots of business people (130) and even a decent number of medical professionals (32) but there are only two scientists (one microbiologist and one physicist). That number might increase by 50 percent if one stem cell researcher has his way.

Raja Kittappa, Ph.D., is running for Congress as a Democrat in Pennsylvania’s 16th District, saying he was convinced he should run by cuts in funding for the National Institutes of Health (NIH).

Kittappa knows about the importance of federal funding for science. He used to work at the NIH where he did some groundbreaking research in isolating the dopamine-generating cells in the brain, the cells that are lost to Parkinson’s disease. His work is now being used by researchers around the world to search for a cure for Parkinson’s.

He also has a personal reason for his research. His grandmother died of Parkinson’s and he feels that any cuts to federal research dollars can have a huge impact on our ability to find new treatments.

“Even one day lost in the fight to cure diseases like the one that afflicted my grandmother is one day too many.”

 Kittappa’s local newspaper picked up his story.

We also have a strong focus on Parkinson’s disease research, spending more than $43 million on 24 different projects.

kevin mccormack

Early clinical trial for ALS looks promising, points to ways to do even better

ALS patient and world famous physicist Stephen Hawking talked with CIRM’s ALS team at Cedars-Sinai last year

The stem cell company Neuralstem had earlier reported promising data from part of the patients enrolled in their phase 1 clinical trial for patients with amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease. Now they have published data for all the patients in the study including the last six who were the first to receive the stem cell injections in the neck instead of the back. More important, three of those last patients received the injections in the full length of their spine, both the neck and back.

The number of patients is small and this is very early data, but the results seem to confirm what seems intuitively obvious: delivering more cells over more area of the spine increases the beneficial effect of the stem cells. Like all phase 1 studies, the primary goal of this trial was to test the safety of the cells and the procedure for injecting them. Both appeared to be uniformly safe. But the team did build measures into the trial that could begin to detect benefit.

The team, split between the University of Michigan and Emory in Atlanta, carefully measured the rate of disease progression prior to the surgery and plotted out an expected rate of decline. They measured several indicators such as grip strength six, nine, 12 and 15 months after the surgery. In half the patients they detected improvement in some of those measures. In the three patients that had stem cells injected in their neck and spine, they detected improvements in several of the measures.

The San Francisco Business Times picked up the company’s press release that quoted the lead researcher from the Emory arm of the study Jonathan Glass on the importance of this first phase:

“We have now shown that the procedure is safe for both lumbar and cervical injections, allowing us to move forward with an aggressive program to test whether this treatment will improve the course of disease for patients with ALS. They have already begun a phase two trial that includes the first two sites plus Massachusetts General Hospital.”

The release also suggests that while the main benefit of the stem cells may be a protective effect preventing further disease damage to the motor nerves, the results showed some level of cell replacement and improvement of the environment in which the nerves are living. These measures will need confirmation in a larger trial.The current work was published in the Annals of Neurology this week.

However, CIRM is funding an effort aimed at upping the ante on the protective benefit. A team at Cedars-Sinai in Los Angeles plans on conducting a trial with stem cells that have been genetically modified to secrete a hormone that has been shown to be protective. They will be using the same surgical equipment and protocol as the current teams, so that aspect of the work should pass the safety test. You can read about that and related CIRM projects on our stem cells for ALS fact sheet.

Don Gibbons