Stem cell treatment helps puppies born with spina bifida walk again

Just when you thought puppies couldn’t get any cuter, this video appears in your twitter feed.

These adorable English bulldog puppies are named Darla and Spanky, and they were born with a birth defect called spina bifida where the bones and tissue surrounding the spinal cord fail to fuse completely. Spina bifida occurs in 1500-2000 children in the US each year and can cause serious problems such as paralysis and issues with walking, cognition, and bladder or bowel control. Dogs born with this condition usually cannot use their hind legs, and as a sad consequence, are typically put down at a young age.

Cutting edge research from UC Davis is now giving these unfortunate puppies hope. Diana Farmer, a fetal surgeon at UC Davis Health, and scientists from the university’s Veterinary Institute for Regenerative Cures have developed a combination surgery and stem cell transplant, using placenta-derived mesenchymal stromal cells (PMSCs), to treat puppies with spina bifida. Because prenatal screening for spina bifida is not done in dogs, Darla and Spanky received the treatment when they were ten weeks old.

With funding from a CIRM preclinical development award, Farmer has done similar surgeries in lambs that are still in the womb. A UC Davis news release provided historical background on Farmer’s work on spina bifida,

“Farmer pioneered the use of surgery prior to birth to improve brain development in children with spina bifida. She later showed that prenatal surgery combined with human placenta-derived mesenchymal stromal cells (PMSCs), held in place with a cellular scaffold, helped research lambs born with the disorder walk without noticeable disability.”

As you can see from the video, the surgeries were a success. Darla and Spanky are now able to live up to their full puppy potential and will live happily ever after with their adoptive family in New Mexico.

Looking forward, Farmer and her team would like to treat more dogs with spina bifida so they can improve another negative consequence of spina bifida called incontinence, or an uncontrollable bladder. The UC Davis release explained that, “while Darla and Spanky are very mobile and doing well on their feet, they still require diapers.” (Side note: this video proves that puppies can make anything look cute, even dirty diapers.)

Additionally, the team is hoping to receive regulatory approval from the US Food and Drug Administration to launch a clinical trial testing this therapy in humans. If this stem cell treatment proves to be both safe and effective in clinical trials, it could potentially prevent spina bifida from ever happening in animals and in humans.

English Bulldog undergoing spina bifida surgery at UC Davis Veterinary Medical Teaching Hospital. (Gregory Urquiaga/UC Davis)

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Treatments, cures and clinical trials: an in-person update on CIRM’s progress

Patients and Patient Advocates are at the heart of everything we do at CIRM. That’s why we are holding three free public events in the next few months focused on updating you on the stem cell research we are funding, and our plans for the future.

Right now we have 33 projects that we have funded in clinical trials. Those range from heart disease and stroke, to cancer, diabetes, ALS (Lou Gehrig’s disease), two different forms of vision loss, spinal cord injury and HIV/AIDS. We have also helped cure dozens of children battling deadly immune disorders. But as far as we are concerned we are only just getting started.

Over the course of the next few years, we have a goal of adding dozens more clinical trials to that list, and creating a pipeline of promising therapies for a wide range of diseases and disorders.

That’s why we are holding these free public events – something we try and do every year. We want to let you know what we are doing, what we are funding, how that research is progressing, and to get your thoughts on how we can improve, what else we can do to help meet the needs of the Patient Advocate community. Your voice is important in helping shape everything we do.

The first event is at the Gladstone Institutes in San Francisco on Wednesday, September 6th from noon till 1pm. The doors open at 11am for registration and a light lunch.

Gladstone Institutes

Here’s a link to an Eventbrite page that has all the information about the event, including how you can RSVP to let us know you are coming.

We are fortunate to be joined by two great scientists, and speakers – as well as being CIRM grantees-  from the Gladstone Institutes, Dr. Deepak Srivastava and Dr. Steve Finkbeiner.

Dr. Srivastava is working on regenerating heart muscle after it has been damaged. This research could not only help people recover from a heart attack, but the same principles might also enable us to regenerate other organs damaged by disease. Dr. Finkbeiner is a pioneer in diseases of the brain and has done ground breaking work in both Alzheimer’s and Huntington’s disease.

We have two other free public events coming up in October. The first is at UC Davis in Sacramento on October 10th (noon till 1pm) and the second at Cedars-Sinai in Los Angeles on October 30th (noon till 1pm). We will have more details on these events in the coming weeks.

We look forward to seeing you at one of these events and please feel free to share this information with anyone you think might be interested in attending.

License to heal: UC Davis deal looks to advance stem cell treatment for bone loss and arthritis

Nancy Lane

Wei Yao and Nancy Lane of UC Davis: Photo courtesy UC Davis

There are many challenges in taking even the most promising stem cell treatment and turning it into a commercial product approved by the Food and Drug Administration (FDA). One of the biggest is expertise. The scientists who develop the therapy may be brilliant in the lab but have little experience or expertise in successfully getting their work through a clinical trial and ultimately to market.

That’s why a team at U.C. Davis has just signed a deal with a startup company to help them move a promising stem cell treatment for arthritis, osteoporosis and fractures out of the lab and into people.

The licensing agreement combines the business acumen of Regenerative Arthritis and Bone Medicine (RABOME) with the scientific chops of the UC Davis team, led by Nancy Lane and Wei Yao.

They plan to test a hybrid molecule called RAB-001 which has shown promise in helping direct mesenchymal stem cells (MSCs) – these are cells typically found in the bone marrow and fat tissue – to help stimulate bone growth and increase existing bone mass and strength. This can help heal people suffering from conditions like osteoporosis or hard to heal fractures. RAB-001 has also shown promise in reducing inflammation and so could prove helpful in treating people with inflammatory arthritis.

Overcoming problems

In a news article on the UC Davis website, Wei Yao, said RAB-001 seems to solve a problem that has long puzzled researchers:

“There are many stem cells, even in elderly people, but they do not readily migrate to bone.  Finding a molecule that attaches to stem cells and guides them to the targets we need provides a real breakthrough.”

The UC Davis team already has approval to begin a Phase 1 clinical trial to test this approach on people with osteonecrosis, a disease caused by reduced blood flow to bones. CIRM is funding this work.

The RABOME team also hopes to test RAB-001 in clinical trials for healing broken bones, osteoporosis and inflammatory arthritis.

CIRM solution

To help other researchers overcome these same regulatory hurdles in developing stem cell therapies CIRM created the Stem Cell Center with QuintilesIMS, a leading integrated information and technology-enabled healthcare service provider that has deep experience and therapeutic expertise. The Stem Cell Center will help researchers overcome the challenges of manufacturing and testing treatments to meet FDA standards, and then running a clinical trial to test that therapy in people.

Life after SPARK: CIRM high school intern gets prestigious scholarship to Stanford

As part of our CIRM scholar blog series, we’re featuring the research and career accomplishments of CIRM funded students.

Ranya Odeh

Ranya Odeh

Meet Ranya Odeh. She is a senior at Sheldon high school in Elk Grove, California, and a 2016 CIRM SPARK intern. The SPARK program provides stem cell research internships to underprivileged high school students at leading research institutes in California.

This past summer, Ranya worked in Dr. Jan Nolta’s lab at UC Davis improving methods that turn mesenchymal stem cells into bone and fat cells. During her internship, Ranya did an excellent job of documenting her journey in the lab on Instagram and received a social media prize for her efforts.

Ranya is now a senior in high school and was recently accepted into Stanford University through the prestigious QuestBridge scholarship program. She credits the CIRM SPARK internship as one of the main reasons why she was awarded this scholarship, which will pay for all four years of her college.

I reached out to Ranya after I heard about her exciting news and asked her to share her story so that other high school students could learn from her experience and be inspired by her efforts.


How did you learn about the CIRM SPARK program?

At my high school, one of our assignments is to build a website for the Teen Biotech Challenge (TBC) program at UC Davis. I was a sophomore my first year in the program, and I didn’t feel passionate about my project and website. The year after, I saw that some of my friends had done the CIRM SPARK internship after they participated in the TBC program. They posted pictures about their internship on Instagram, and it looked like a really fun and interesting thing to do. So I decided to build another website (one that I was more excited about) in my junior year on synthetic biology. Then I entered my website in the TBC and got first prize in the Nanobiotechnology field. Because I was one of the winners, I got the SPARK internship.

What did you enjoy most about your SPARK experience?

For me, it was seeing that researchers aren’t just scientists in white lab coats. The Nolta lab (where I did my SPARK internship) had a lot of personality that I wasn’t really expecting. Working with stem cells was so cool but it was also nice to see at the same time that people in the lab would joke around and pull pranks on each other. It made me feel that if I wanted to have a future in research, which I do, it wouldn’t be doing all work all the time.

What was it like to do research for the first time?

Ranya taking care of her stem cells!

Ranya taking care of her stem cells!

The SPARK internship was my first introduction to research. During my first experiment, I remember I was changing media and I thought that I was throwing my cells away by mistake. So I freaked out, but then my mentor told me that I hadn’t and everything was ok. That was still a big deal and I learned a lesson to ask more questions and pay more attention to what I was doing.

Did the SPARK program help you when you applied to college?

Yes, I definitely feel like it did. I came into the internship wanting to be a pharmacist. But my research experience working with stem cells made me want to change my career path. Now I’m looking into a bioengineering degree, which has a research aspect to it and I’m excited for that. Having the SPARK internship on my college application definitely helped me out. I also got to have a letter of recommendation from Dr. Nolta, which I think played a big part as well.

Tell us about the scholarship you received!

I got the QuestBridge scholarship, which is a college match scholarship for low income, high achieving students. I found out about this program because my career counselor gave me a brochure. It’s actually a two-part scholarship. The first part was during my junior year of high school and that one didn’t involve a college acceptance. It was an award that included essay coaching and a conference that told you about the next step of the scholarship.

The second part during my senior year was called the national college match scholarship. It’s an application on its own that is basically like a college application. I submitted it and got selected as a finalist. After I was selected, they have partner colleges that offer full scholarships. You rank your choice of colleges and apply to them separately with a common application. If any of those colleges want to match you and agree to pay for all four years of your college, then you will get matched to your top choice. There’s a possibility that more than one college would want to match you, but you will only get matched with the one that you rank the highest. That was Stanford for me, and I am very happy about that.

Why did you pick Stanford as your top choice?

It’s the closest university to where I grew up that is very prestigious. It was also one of the only colleges I’ve visited. When I was walking around on campus, I felt I could see myself there as a student and with the Stanford community. Also, it will be really nice to be close to my family.

What do you do in your free time?

I don’t have a lot of free time because I’m in Academic Decathalon and I spend most of my time doing that. When I do have free time, I like to watch Netflix, blogs on YouTube, and I try to go to the gym [laughs].

Did you enjoy posting about your SPARK internship on Instagram?

I had a lot of fun posting pictures of me in the lab on Instagram. It was also nice during the summer to see other SPARK students in different programs talk about the same things. We shared jokes about micropipettes and culturing stem cells. It was really cool to see that you’re not the only one posting nerdy science pictures. I also felt a part of a larger community outside of the SPARK program. Even people at my school were seeing and commenting on what I was doing.

UC Davis CIRM SPARK program 2016

UC Davis CIRM SPARK program 2016

I also liked that I got feedback about what I was doing in the lab from other SPARK students. When I posted pictures during my internship, I talked about working with mesenchymal stem cells. Because we all post to the same #CIRMSPARKlab hashtag, I saw students from CalTech commenting that they worked with those stem cells too. That motivated me to work harder and accomplish more in my project. Instagram also helped me with my college application process. I saw that there were other students in the same position as me that were feeling stressed out. We also gave each other feedback on college essays and having advice about what I was doing really helped me out.

Do you think it’s important for students to be on social media?

Yes, I think it’s important with boundaries of course. There are probably some people who are on social media too often, and you should have a balance. But it’s nice to see what other students are doing to prepare for college and to let loose and catch up with your friends.

What advice would you give to younger high school students about pursuing science?

I feel like students can’t expect things to be brought to them. If they are interested in science, they need to take the initiative to find something that they are going to want to do. The CIRM internship was brought to my attention. But I have friends that were interested in medicine and they found their own internships and ways to learn more about what they wanted to do. So my advice is to take initiative and not be scared of rejection, because if you’re scared of rejection you’re not going to do anything.

To hear more about Ranya’s SPARK internship experience, read her blog “Here’s what you missed this summer on the show coats.” You can also follow her on Instagram and Twitter. For more information about the CIRM SPARK internship program, please visit the CIRM website.


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Trash talking and creating a stem cell community

imilce2

Imilce Rodriguez-Fernandez likes to talk trash. No, really, she does. In her case it’s cellular trash, the kind that builds up in our cells and has to be removed to ensure the cells don’t become sick.

Imilce was one of several stem cell researchers who took part in a couple of public events over the weekend, on either side of San Francisco Bay, that served to span both a geographical and generational divide and create a common sense of community.

The first event was at the Buck Institute for Research on Aging in Marin County, near San Francisco. It was titled “Stem Cell Celebration” and that’s pretty much what it was. It featured some extraordinary young scientists from the Buck talking about the work they are doing in uncovering some of the connections between aging and chronic diseases, and coming up with solutions to stop or even reverse some of those changes.

One of those scientists was Imilce. She explained that just as it is important for people to get rid of their trash so they can have a clean, healthy home, so it is important for our cells to do the same. Cells that fail to get rid of their protein trash become sick, unhealthy and ultimately stop working.

Imilce is exploring the cellular janitorial services our bodies have developed to deal with trash, and trying to find ways to enhance them so they are more effective, particularly as we age and those janitorial services aren’t as efficient as they were in our youth.

Unlocking the secrets of premature aging

Chris Wiley, another postdoctoral researcher at the Buck, showed that some medications that are used to treat HIV may be life-saving on one level, preventing the onset of full-blown AIDS, but that those benefits come with a cost, namely premature aging. Chris said the impact of aging doesn’t just affect one cell or one part of the body, but ripples out affecting other cells and other parts of the body. By studying the impact those medications have on our bodies he’s hoping to find ways to maintain the benefits of those drugs, but get rid of the downside.

Creating a Community

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Across the Bay, the U.C. Berkeley Student Society for Stem Cell Research held it’s 4th annual conference and the theme was “Culturing a Stem Cell Community.”

The list of speakers was a Who’s Who of CIRM-funded scientists from U.C. Davis’ Jan Nolta and Paul Knoepfler, to U.C. Irvine’s Henry Klassen and U.C. Berkeley’s David Schaffer. The talks ranged from progress in fighting blindness, to how advances in stem cell gene editing are cause for celebration, and concern.

What struck me most about both meetings was the age divide. At the Buck those presenting were young scientists, millennials; the audience was considerably older, baby boomers. At UC Berkeley it was the reverse; the presenters were experienced scientists of the baby boom generation, and the audience were keen young students representing the next generation of scientists.

Bridging the divide

But regardless of the age differences there was a shared sense of involvement, a feeling that regardless of which side of the audience we are on we all have something in common, we are all part of the stem cell community.

All communities have a story, something that helps bind them together and gives them a sense of common purpose. For the stem cell community there is not one single story, there are many. But while those stories all start from a different place, they end up with a common theme; inspiration, determination and hope.

 

A Dream made me change my mind. Almost.

Dream Alliance

Dream Alliance: photo courtesy Daily Telegraph, UK

On Friday I was faced with the real possibility that a horse had made an ass out of me.

Over the years we have written many articles about the risks of unproven stem cell therapies, treatments that have not yet been shown in clinical trials to be safe and effective. Often we have highlighted the cases of high profile athletes who have undergone stem cell treatments for injuries when there is little evidence that the treatments they are getting work.

Well, on Friday I saw an athlete who bounced back from a potentially career-ending injury to enjoy an amazing career thanks to a stem cell treatment. I wondered if I was going to have to revise my thoughts on this topic. Then my wife pointed out to me that the athlete was a horse.

We had been watching the movie Dark Horse, a truly delightful true story about a group of working class people in a Welsh mining village who bred and raised a horse that went on to great success as a race horse – often beating out thoroughbreds that were worth millions of dollars.

 

At one point the horse, Dream Alliance, suffered an almost fatal injury. Everyone assumed his career was over. But thanks to a stem cell treatment he was able to return to the track and became the first horse to win a major race after undergoing stem cell surgery.

It shouldn’t be too surprising that stem cells can help heal serious injuries in horses, the researchers at UC Davis have been using them to help treat horses for years – with great success. The danger comes in then assuming that just because stem cells work for horses, they’ll work for people. And that if they can cure one kind of injury, why not another.

That thought was driven home to me on Saturday when I was giving a talk to a support group for ALS or Lou Gehrig’s disease. ALS is a nasty, rapidly progressive disease that attacks the motor nerve cells in the brain and spinal cord, destroying a person’s ability to move, eat, speak or breath.

One person asked about a clinic they had been talking to which claimed it might be able to help them. The clinic takes fat from the person with ALS, isolates the stem cells in the fat and injects it back into the person. The clinic claims it’s been very effective in treating injuries such as torn muscles, and that it also works for other problems like Parkinson’s so it might help someone with ALS.

And that’s the problem. We hear about one success story that seems to prove stem cells can do amazing things, and then we are tempted to hope that if it works for one kind of injury, it might work for another, or even for a neurodegenerative disease.

And hope doesn’t come cheap. The cost of the procedure was almost $10,000.

If you have a disease like ALS for which there is no cure, and where the life expectancy is between two to five years, you can understand why someone would be tempted to try anything, no matter how implausible. What is hard is when you have to tell them that without any proof that it works, and little scientific rational as to why it would work, that it’s hard to recommend they try using their own fat cells to treat their ALS.

At CIRM we are investing more than $56.5 million in 21 different projects targeting ALS.   We are hopeful one of them, Clive Svendsen’s research at Cedars-Sinai Medical Center,  will soon get approval from the FDA to start a clinical trial.

Much as we would like to believe in miracles, medical breakthroughs usually only come after years of hard, methodical work. It would be great if injecting your own fat-derived stem cells into your body could cure you of all manner of ailments. But there’s no evidence to suggest it will.

The movie Dark Horse shows that for one horse, for one group of people in a small Welsh mining village, stem cells helped create a happy ending. We are hoping stem cells will one day offer the same sense of hope and possibility for people battling deadly diseases like ALS. But that day is not yet here.

 

 

Brave new world or dark threatening future: a clear-eyed look at genome editing and what it means for humanity

Frankenstein

   Is this the face of the future?

“Have you ever wished that there were something different about yourself? Maybe you imagined yourself taller, thinner or stronger? Smarter? More attractive? Healthier?”

That’s the question posed by UC Davis stem cell researcher (and CIRM grantee) Paul Knoepfler at the start of his intriguing new book ‘GMO Sapiens: The Life-Changing Science of Designer Babies’.

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You can find GMO Sapiens on Amazon.com

The book is a fascinating, and highly readable, and takes a unique look at the dramatic advances in technology that allow us to edit the human genome in ways that could allow us to do more than just create “designer babies”, it could ultimately help us change the definition of what it means to be human.

Paul begins by looking at the temptation to use technologies like CRISPR (we have blogged about this here), to genetically edit or alter human embryos so that the resulting child is enhanced in some ways. It could be that the editing is used to remove a genetic mutation that could cause a deadly disease (such as the BRCA1 gene that puts women at increased risk of breast and ovarian cancer) or it could be that the technique is used to give a baby blue eyes, to make it taller, more athletic, or to simply eliminate male pattern baldness later in life.

Paul says those latter examples are not as ridiculous as they sound:

Paul Knoepfler

Paul Knoepfler

“If you think these ideas sound far-fetched, consider that Americans alone spend tens of billions of dollars each year on plastic surgery procedures and creams to try to achieve these kinds of goals. Some of the time elective cosmetic surgery is done on children. In the future, we might have “cosmetic genetic surgeons” who do “surgery” on our family’s genes for cosmetic reasons. In other countries the sensibilities and cultural expectations could lead to other kinds of genetic modifications of humans for “enhancements”.

While the technology that enables us to do this is new, the ideas behind why we would want to do this are far from new. Paul delves into those ideas including a look at the growth of the eugenics movement in the late 19th and early 20th century advocating the improvement of human genetic traits through higher reproductive rates for people considered “superior”. And there was a darker side to the movement:

“Indiana had instituted the first law for sterilization of “inferior” people in the world in 1907. Astonishingly this state law and then similar laws (the original was revoked, but a new law was passed later) stayed on the books in that state until 1974.

This led to approximately 2,500 governmentally forced sterilizations. The poor, uneducated, people of color, Native Americans, and people with disabilities were disproportionately targeted.”

Paul explores the ethical and moral implications of changing our genetic code, changes that can then be passed on to future generations. While he understands the desire to use these technologies to create positive changes, he is also very clear in his concerns that we don’t yet have enough knowledge to be able to use them in a safe manner.

“CRISPR can literally re-write the genomic book inside of us. However, it remains unknown how often it might go to the wrong page or paragraph, so to speak, or stay on the right page, but make an undesired edit there.”

Tiny errors in editing the genome, particularly at such an early stage in an embryo’s development, could have profound and unintended consequences years down the road, resulting in physical or developmental problems we can’t anticipate or predict. For example, you might remove the susceptibility to one disease only to create an even larger problem, one that is now embedded in that person’s DNA and ready to be passed on to subsequent generations.

The book includes interviews with key figures in the field – scientists, bioethicists etc. – and covers a wide range of views of what we should do. For example, the Director of the US National Institutes of Health (NIH), Francis Collins, said that designer babies “make good Hollywood — and bad science,” while the Center for Genetics and Society has advocated for a moratorium on human genetic modification in the US.

In contrast, scientists such as Harvard professor George Church and CRISPR pioneer Jennifer Doudna of UC Berkeley, say we need to carefully explore how to harness the potential for these technologies.

For Church it is a matter of choice:

“The new technology enables parents to make choices about their children just as they might with Ritalin or cleft palate surgery to ‘improve’ behavior or appearance.”

For Doudna it’s acknowledging the fact that you can’t put the genie back in the bottle:

“There’s no way to unlearn what is learned. We can’t put this technology to bed. If a person has basic knowledge of molecular biology they can do it. It’s not realistic to think we can block it…We want to put out there the information that people would need to make an informed decision, to encourage appropriate research and discourage forging ahead with clinical applications that could be dangerous or raise ethical issues.”

The power of Paul’s book is that while it does not offer any easy answers, it does raise many important questions.

It’s a wonderfully well-written book that anyone can read, even someone like me who doesn’t have a science background. He does a good job of leading the reader through the development of these technologies (from the basic idea of genetically altering plants to make them disease resistant) to the portrayal of these concepts in literature (Frankenstein and Brave New World) to movies (Gattaca – 4 stars on Rotten Tomatoes  a great film if you haven’t already seen it).

It’s clear where Paul stands on the issue; he believes there should be a moratorium on human genetic modification until we have a much deeper understanding of the science behind it, and the ethics and morality underpinning it:

“This is a very exciting time to be alive and we should be open to embracing change, but not blindly or in a rush. Armed with information and passion, we can have a major, positive impact on how this biotech revolution unfolds and impacts humanity.”

By the way, Paul also has one of the most widely read blogs about stem cells, where you can read more about his thoughts on CRISPR and other topics.

 

Rare disease underdogs come out on top at CIRM Board meeting

 

It seems like an oxymoron but one in ten Americans has a rare disease. With more than 7,000 known rare diseases it’s easy to see how each one could affect thousands of individuals and still be considered a rare or orphan condition.

Only 5% of rare diseases have FDA approved therapies

rare disease

(Source: Sermo)

People with rare diseases, and their families, consider themselves the underdogs of the medical world because they often have difficulty getting a proper diagnosis (most physicians have never come across many of these diseases and so don’t know how to identify them), and even when they do get a diagnosis they have limited treatment options, and those options they do have are often very expensive.  It’s no wonder these patients and their families feel isolated and alone.

Rare diseases affect more people than HIV and Cancer combined

Hopefully some will feel less isolated after yesterday’s CIRM Board meeting when several rare diseases were among the big winners, getting funding to tackle conditions such as ALS or Lou Gehrig’s disease, Severe Combined Immunodeficiency or SCID, Canavan disease, Tay-Sachs and Sandhoff disease. These all won awards under our Translation Research Program except for the SCID program which is a pre-clinical stage project.

As CIRM Board Chair Jonathan Thomas said in our news release, these awards have one purpose:

“The goal of our Translation program is to support the most promising stem cell-based projects and to help them accelerate that research out of the lab and into the real world, such as a clinical trial where they can be tested in people. The projects that our Board approved today are a great example of work that takes innovative approaches to developing new therapies for a wide variety of diseases.”

These awards are all for early-stage research projects, ones we hope will be successful and eventually move into clinical trials. One project approved yesterday is already in a clinical trial. Capricor Therapeutics was awarded $3.4 million to complete a combined Phase 1/2 clinical trial treating heart failure associated with Duchenne muscular dystrophy with its cardiosphere stem cell technology.  This same Capricor technology is being used in an ongoing CIRM-funded trial which aims to heal the scarring that occurs after a heart attack.

Duchenne muscular dystrophy (DMD) is a genetic disorder that is marked by progressive muscle degeneration and weakness. The symptoms usually start in early childhood, between ages 3 and 5, and the vast majority of cases are in boys. As the disease progresses it leads to heart failure, which typically leads to death before age 40.

The Capricor clinical trial hopes to treat that aspect of DMD, one that currently has no effective treatment.

As our President and CEO Randy Mills said in our news release:

Randy Mills, Stem Cell Agency President & CEO

Randy Mills, Stem Cell Agency President & CEO

“There can be nothing worse than for a parent to watch their child slowly lose a fight against a deadly disease. Many of the programs we are funding today are focused on helping find treatments for diseases that affect children, often in infancy. Because many of these diseases are rare there are limited treatment options for them, which makes it all the more important for CIRM to focus on targeting these unmet medical needs.”

Speaking on Rare Disease Day (you can read our blog about that here) Massachusetts Senator Karen Spilka said that “Rare diseases impact over 30 Million patients and caregivers in the United States alone.”

Hopefully the steps that the CIRM Board took yesterday will ultimately help ease the struggles of some of those families.

CIRM Scholar Jessica Gluck on using stem cells to make biological pacemakers for the heart

As part of our CIRM scholar series, we feature the research accomplishments of students and postdocs that have received CIRM funding.

Jessica Gluck, CIRM Scholar

Jessica Gluck, CIRM Scholar

I’d like to introduce you to one of our CIRM Scholars, Jessica Gluck. She’s currently a Postdoctoral Fellow at UC Davis working on human stem cell models of heart development. Jessica began her education in textiles and materials science at North Carolina State University, but that developed into a passion for biomedical engineering and stem cell research, which she pursued during her PhD at UC Los Angeles. During her graduate research, Jessica developed 3D bio-scaffolds that help human stem cells differentiate into functioning heart cells.

We asked Jessica to discuss her latest foray in the fields of stem cells and heart development.


Q: What are you currently working on in the lab?

JG: I work as a postdoc at UC Davis in the lab of Deborah Lieu. She’s working on developing pacemaking cardiomyocytes (heart cells) from human induced pluripotent stem cells (iPS cells). Pacemaking cells are the cells of the heart that are in charge of rhythm and synchronicity. Currently, we’re able to take iPS cells and get them to a cardiomyocyte state, but we want to further develop them into a pacemaking cell.

So ultimately, we’re trying to make a biological pacemaker. We can figure out how we can make a cell become the cell that tells your heart to beat, and there’s two things we can get out of that. First, if we understand how we get these beating cells, the ones that are telling the other heart cells to beat, we might be able to understand how different heart diseases progress, and we might be able to come up with a new way to prevent or treat that disease. Second, if we understand how we’re getting these pacemaking cells, we could hopefully bioengineer a biological pacemaker so you wouldn’t necessarily need an electronic pacemaker. With a biological one, a patient wouldn’t have to go back to the doctor to have their battery replaced. And they wouldn’t have to have multiple follow up surgeries throughout their life.

Q: What models are you using to study these pacemaking cells?

JG: I’m looking at my project from two different directions. On one side, we’re using a pig model, and we’re isolating cells from the sinoatrial (SA) node, which is where the pacemaking cells actually reside in your heart. And there’s really not that many of these cells. You probably have about a billion cells in your heart, but there’s maybe 100,000 of these pacemaking cells that are actually controlling the uniform beating of the heart. So we’re looking at the native SA node in the pig heart to see if it’s structurally any different than ventrical or atrial heart tissue.

Diagram of the heart depicting the Sinoatrial Node. (Image from Texas Heart Institute.

Diagram of the heart depicting the Sinoatrial Node. (Image from Texas Heart Institute)

We’ve found that the SA node is definitely different. So we’re de-cellularizing that tissue (removing the cells but not the matrix, or support structure, that keeps them in place) thinking that we could use the native matrix as a scaffold to help guide these heart cells to become the pacemaking phenotype. On the other side, we’re taking dishes with a known elasticity and we’re coating them with different proteins to see if we can tease out if there’s something that an individual protein does or a certain stiffness that actually is part of the driving force of making a pacemaking cell. We’ve gotten some pretty good preliminary results. So hopefully the next phase will be seeing how functional the cells are after they’ve been on these de-cellularized matrices.

Q: Why does your lab work with pig models?

JG: Pig hearts are pretty close to the human heart – their anatomy is pretty similar. To give you context, a pig heart is slightly larger than the size of your two hands clasped together. But the SA node, when you isolate it out, is only a couple of millimeters squared. It’s a lot smaller than we originally thought, and if we had gone with a smaller animal model, we wouldn’t be able to tangibly study or manipulate the SA node area. Because we are at UC Davis, we have a Meat Lab on campus, and we are able to get the pig hearts from them.

Q: Have you run into any road blocks with your research?

JG: For anybody that’s working with cardiomyocytes, the biggest problem is getting stem cells to become mature cardiomyocytes. Some labs have shown that you can get cells to a more mature cardiomyocyte after it’s been in culture for almost 100 days, but that’s not exactly feasible or that helpful.

We’ve been able to isolate out a small population of cells that we’re pretty sure are pacemaking cells. Over the last year, we’ve realized that a lot of the information that we thought we knew about pacemaking cells isn’t necessarily specific to pacemaking cells. Many of the biological markers that people have published in the literature are present in pacemaking cells, but we realized that they are also present in other heart cells like atrial cells, just in a lower amount. So we haven’t really been able to pick one specific biomarker that we’ve been able to say, yes this is actually a pacemaking cell. Instead, we have a small percentage of cells that we’re able to study. But we’re trying to figure out if there’s a way that we could increase our yield, or if there’s something fundamentally different about the environment that would also increase the yield of these pacemaking cells. So we’ve had a lot of trouble shooting along the way.

Q: What was your experience like as a CIRM scholar?

JG: I became a CIRM scholar in the spring of 2014. It was through the UC Davis Stem Cell Training Program. The opportunity was very helpful for me because it was in my first year as a postdoc at Davis. I earned my PhD at UCLA, so I was dealing with being on a new campus, trying to figure out whose lab I could go to to borrow random things and where to find equipment that I needed to use. So it was helpful to be around a group of other people that were also doing stem cell projects. Even though a lot of us were focused on different areas, it was still helpful to talk to other people, especially if you get somebody’s perspective that isn’t necessarily in your field. They might come up with a random idea that you haven’t thought of before.

Over the course of the year, we had a journal club, which was always interesting to see what’s going on in the field. I also went to the annual International Society for Stem Cell Research meeting in Vancouver using CIRM funding. And as part of the program, we also worked with the CIRM Bridges program between UC Davis and Cal State Sacramento. There were Bridges master’s students that were there with us. It was interesting to hear their take on everything, and they were very enthusiastic. We have had two master’s students work in our lab. I think it was very beneficial to them because they got a lot of hands on training and both have gone on to jobs in the regenerative medicine field.

Q: What is the future of stem cell research?

JG: If you’re looking at heart disease and stem cell treatments, there’s been some interesting clinical trials that have come out that have some promising results. I think that for a couple of those studies, people might have jumped the gun a little getting the treatments into the clinic. There’s still a lot that people should study in the lab before we move on to clinical trials. But I do think that we will see something in the next 20 years where stem cell research is going to have a huge therapeutic benefit. The field is just moving so quickly, and I think it will be really interesting to see what advances are made.

For our research, I’ve always been fairly realistic, and unfortunately, I don’t think we will see this biological pacemaker any time soon. But I think that the research that we produce along the way will be very beneficial to the field and our work will hopefully improve the foundation of what is known about pacemaking cells. What I think is really interesting about our lab’s work, is that we are moving into a 3D culture environment. Cells behave very differently in the body as opposed to on a plastic petri dish. So I think it’s very encouraging that we are seeing a lot more labs moving towards a more physiologically relevant model.

Q: What are your future goals?

I’ve been lucky that I’ve been able to work with very well established professors and also brand new faculty. But I’ve seen how difficult the funding climate is – it’s very daunting. So I’m really not sure what will happen next, and I’m keeping my options open.

I’ve really enjoyed working with our undergraduate and graduate students. I’ve gotten involved with outreach programs in Sacramento that promote science to young kids. It’s something that I’ve really enjoyed, and it’s very interesting telling people that I work in stem cells. Middle school kids seem to think that stem cells are magic. It’s fun to explain the very basics of stem cells and to see the light bulb moment where they understand it. I’m hoping to end up in a career that is still within the stem cell field but more towards teaching or outreach programs.

Q: What is your favorite thing about being a scientist?

JG: The thing I really like is having a puzzle that you’re trying to figure out the answer to. It’s great because every time you answer one question, that answer is going to lead you to at least three or four more new questions. I think that that’s really interesting especially trying to figure out how all the puzzle pieces fit together, and I’ve really enjoyed getting to work with people in very different fields. My parents think its funny because they said even as a little kid, I hated not knowing the answers to questions – and still do! They were completely understanding as to why I stayed in school as long as I did.

You can learn more about Jessica’s research by following her on Twitter: @JessicaGluckPhD

Patients beware: warnings about shady clinics and suspect treatments

stem-cells therapy?

Every day we get a call from someone seeking help. Some are battling a life-threatening or life-changing disease. Others call on behalf of a friend or loved one. All are looking for the same thing; a treatment, better still a cure, to ease their suffering.

Almost every day we have to tell them the same thing; that the science is advancing but it’s not there yet. You can almost feel the disappointment, the sense of despair, on the other end of the line.

If it’s hard for us to share that news, imagine how much harder it is for them to hear it. Usually by the time they call us they have exhausted all the conventional therapies. In some cases they are not just running out of options, they are also running out of time.

Chasing hope

Sometimes people mention that they went to the website of a clinic that was offering treatments for their condition, claiming they had successfully treated people with that disease or disorder. This week I had three people mention the same clinic, here in the US, that was offering them “treatments” for multiple sclerosis, traumatic brain injury and chronic obstructive pulmonary disease (COPD). Three very different problems, but the same approach was used for each one.

It’s easy to see why people would be persuaded that clinics like this could help them. Their websites are slick and well produced. They promise to take excellent care of patients, often helping take care of travel plans and accommodation.

There’s just one problem. They never offer any scientific evidence on their website that the treatments they offer work. They have testimonials, quotes from happy, satisfied patients, but no clinical studies, no results from FDA-approved clinical trials. In fact, if you explore their sites you’ll usually find an FAQ section that says something to the effect of they are “not offering stem cell therapy as a cure for any condition, disease, or injury. No statements or implied treatments on this website have been evaluated or approved by the FDA. This website contains no medical advice.”

What a damning but revealing phrase that is.

Now, it may be that the therapies they are offering won’t physically endanger patients – though without a clinical trial it’s impossible to know that – but they can harm in other ways. Financially it can make a huge dent in someone’s wallet with many treatments costing $10,000 or more. And there is also the emotional impact of giving someone false hope, knowing that there was little, if any, chance the treatment would work.

Shining a light in shady areas

U.C. Davis stem cell researcher, CIRM grantee, and avid blogger Paul Knoepfler, highlighted this in a recent post for his blog “The Niche” when he wrote:

Paul Knoepfler

Paul Knoepfler

“Patients are increasingly being used as guinea pigs in the stem cell for-profit clinic world via what I call stem cell shot-in-the-dark procedures. The clinics have no logical basis for claiming that these treatments work and are safe.

As the number of stem cell clinics continues to grow in the US and more physicians add on unproven stem cell injections into their practices as a la carte options, far more patients are being subjected to risky, even reckless physician conduct.”

As if to prove how real the problem is, within hours of posting that blog Paul posted another one, this time highlighting how the FDA had sent a Warning Letter to the Irvine Stem Cell Treatment Center saying it had serious concerns about the way it operates and the treatments it offers.

Paul has written about these practices many times in the past, sometimes incurring the wrath of the clinic owners (and very pointed letters from their lawyers). It’s to his credit that he refuses to be intimidated and keeps highlighting the potential risks that unapproved therapies pose to patients.

Making progress

As stem cell science advances we are now able to tell some patients that yes, there are promising therapies, based on good scientific research, that are being tested in clinical trials.

There are not as many as we would like and none have yet been approved by the FDA for wider use. But those will come in time.

For now we have to continue to work hard to raise awareness about the need for solid scientific evidence before more people risk undergoing an unproven stem cell therapy.

And we have to continue taking calls from people desperate for help, and tell them they have to be patient, just a little longer.

***

If you are considering a stem cell treatment, the International Society for Stem Cell Research had a terrific online resource, A Closer Look at Stem Cells. In particular, check out the Nine Things to Know about Stem Cell Treatments page.