A patient perspective on how stem cells could give a second vision to the blind

October is Blindness Awareness month. In honor of the patients who suffer from diseases of blindness and of the scientists and doctors who work tirelessly to develop treatments and cures for these diseases, we are featuring an interview with Kristin Macdonald, a woman who is challenged by Retinitis Pigmentosa (RP).

RP is a genetically inherited disease that affects the photoreceptors at the back of the eye in an area called the retina. It’s a hard disease to diagnose because the first signs are subtle. Patients slowly lose their peripheral vision and ability to see well at night. As the disease progresses, the window of sight narrows and patients experience “tunnel vision”. Eventually, they become totally blind. Currently, there is no treatment for RP, but stem cell research might offer a glimmer of hope.

Kristin MacDonald

Kristin MacDonald

Kristin Macdonald was the first patient treated in a CIRM-funded stem cell trial for RP run by Dr. Henry Klassen at UC Irvine. She is a patient advocate and inspirational speaker for the blind and visually impaired, and is also a patient ambassador for Americans for Cures. Kristin is an amazing woman who hasn’t let RP prevent her from living her life. It was my pleasure to interview her to learn more about her life’s vision, her experience in CIRM’s RP trial, and her thoughts on patient advocacy and the importance of stem cell research.


Q: Tell us about your experience with being diagnosed with RP?

I was officially diagnosed with RP at 31. RP is a very difficult thing to diagnose, and I had to go through a series of doctors before we figured it out. The signs were there in my mid-to-late twenties, but unfortunately I didn’t really know what they were.

Being diagnosed with RP was really surprising to me. I grew up riding horses and doing everything. I had 20/20 vision and didn’t need any reading glasses. I started getting these night vision symptoms in my mid-to-late 20s in New York when I was in Manhattan. It was then that I started tripping, falling and getting clumsy. But I didn’t know what was happening and I was having such a great time with my life that I just denied it. I didn’t want to acknowledge that anything was wrong.

So I moved out to Los Angeles to pursue an acting and television career, and I just kept ignoring that thing in the brain that says “something’s wrong”. By the time I broke my arm for the second time, I had to go to see a doctor. And that’s when they diagnosed me.

Q: How did you boost yourself back up after being diagnosed with RP?

RP doesn’t come with an instruction booklet. It’s a very gradual adjustment emotionally, physically and spiritually. The first thing I did was to get out of denial, which was a really scary place to be because you can break your leg that way. You have to acknowledge what’s happening in life otherwise you’ll never get anywhere or past anything. That was my first stage of getting over denial. As I slowly started to accept things, I learned to live in the moment, which in a way is a big thing in life because we should all be living for today.

I think the fear of someone telling you that you’re going to go into the dark when you’ve always lived your life in the light can be overwhelming at times. I used to go to the mall and sometimes a door to a store would be gone or an elevator that I used to see is gone. What I did to deal with these fears and changes was to become as proactive as possible. I enlisted all of the best people around me in the business. I started doing charitable work for the Center for the Partially Sighted and for the Foundation for Fighting Blindness. I sat on the board of AIRSLA.org, an internet radio service for the blind and visually impaired, where I still do my radio show. Through that, I met other people who were going through the same type of thing and would come into my home to teach me independent living skills.

I remember the first day when an independent living counselor from the Center for the Partially Sighted came to my house and said we have to check in and see what your adjustment to blindness is like. Those words cut through me. “Adjustment to blindness”. It felt like I was going to prison, that’s how it felt like to me back then. But I am so glad I reached out to the Center for the Partially Sighted because they gave me invaluable instructions on how to function as a blind person. They helped me realize I could really live a good life and be whole, and that blindness would never define me.

I also worked a lot on my spiritual side. I read a lot of positive thinking books and found comfort in my faith in god and the support from my family, friends and my boyfriend. I can’t even enumerate how good they’ve been to me.

Q: How has being blind impacted your ability to do the things you love?

I’m a very social person, so giving up my car and suddenly being confined at night was crushing to me. And we didn’t have Uber back then! During that time, I had to learn how to lead a full life socially. I still love to do salsa dancing but it’s tricky. If I stand on the sidelines, some of the dancers will pass you by because they don’t know you’re blind. I also learned how to horseback ride and swim in the ocean – just a different way. I go in the water on a surf leash. Or I ride around the ring with my best friend guiding me.

Kristin loves to ride horses.

Kristin doesn’t let being mostly blind stop her from riding horses.

Q: What treatments have you had for RP?

I investigated just about everything that was out there. [Laughs] After I was diagnosed, I became very proactive to find treatments. But after a while, I became discouraged because these treatments either didn’t work or still needed time for the FDA to give approval.

I did participate in a study nine years ago and had genetically modified cells put into my eye. I had two surgeries: one to put the cells in and one to take them out because the treatment hadn’t done anything. I didn’t get any improvement, and that was crushing to me because I had hoped and waited so long.

I just kept praying, waiting, reading and hoping. And then boom, all the sudden I got a phone call from UC Irvine saying they wanted me to participate in their stem cell trial for RP. They said I’d be the third person in the world to have it done and the first in their clinical trial. They told me I was to be the first North American patient to have progenitor cells put in my eye, which is pretty amazing.

Q: Was it easy to decide to participate in the UC Irvine CIRM-funded trial?

Yes. But don’t get me wrong, I’m human. I was a little scared. It’s a new thing and you have to sign papers saying that you understand that we don’t exactly know what the results will be. Essentially, you are agreeing to be a pathfinder.

Luckily, I have not had any adverse effects since the trial. But I’ve always had a great deal of faith in stem cells. For years, I’ve been hearing about it and I’ve always put my hopes in stem cells thinking that that’s going to be the answer for blindness.

Q: Have you seen any improvements in your sight since participating in this trial?

I was treated a year ago in June. The stem cell transplant was in my left eye, my worse eye that has never gotten better. It’s been about 15 months now, and I started to see improvement after about two months following the treatment. When I would go into my bathroom, I noticed that it was a lot brighter. I didn’t know if I was imagining things, but I called a friend and said, “I don’t know if I’m imagining things but I’m getting more light perception in this eye.”

Sure enough, over a period of about eight months, I had gradual improvement in light perception. Then I leveled off, but now there is no question that I’m photo sensitive. When I go out, I use my sunglasses, and I see a whole lot more light.

Because I was one of the first patients in the trial, they had to give me a small dose of cells to test for safety. So it was amazing that a smaller dose of cells was still able to help me gain back some sight! One of the improvements that I’ve had is that I can actually see the image of my finger waving back and forth on my left side, which I couldn’t before when I put mascara on. I say this because I have put lip pencil all over my mouth by accident. That must have been a real sight! For a woman, putting on makeup is really important.

Q: What was your experience like participating in the UC Irvine trial?

Dr. Klassen who runs the UC Irvine stem cell trial for RP is an amazing person. He was in the room with me during the transplant procedure. I have such a high regard and respect for Dr. Klassen because he’s been working on the cure for RP as long as I’ve had it. He’s someone who’s dedicated his life to trying to find an answer to a disease that I’ve been dealing with on a day-to-day basis.

Dr. Klassen had the opportunity to become a retinal surgeon and make much more money in a different area. But because it was too crushing to talk to patients and give them such a sad diagnosis, he decided he was going to do something about it. When I heard that, I just never forgot it. He’s a wonderful man and he’s really dedicated to this cause.

Q: How have you been an advocate for RP and blindness?

I’ve been an advocate for the visually impaired in many different aspects. I have raised money for different research foundations and donated my time as a host and an MC to various charities through radio shows. I’ve had a voice in the visually impaired community in one way or another on and off for 15 years.

I also started getting involved in Americans for Cures only a few months ago. I am helping them raise awareness about Proposition 71, which created CIRM, and the importance of funding stem cell research in the future.

I may in this lifetime get actual vision again, a real second vision. But in the meantime, I’ve been working on my higher self, which is good because a friend of mine who is totally blind reminded me today, “Kristin, just remember, don’t live for tomorrow just getting that eye sight back”. My friend was born blind. I told him he is absolutely right. I know I can lead a joyful life either way. But trust me, having a cure for RP would be the icing on the cake for me.

Q: Why is it important to be a patient advocate?

I think it’s so important from a number of different aspects, and I really felt this at the International Society for Stem Cell Research (ISSCR) conference in San Francisco this summer when certain people came to talk to me afterwards, especially researchers and scientists. They don’t get to see the perspective of the patient because they are on the other side of the fence.

I think it’s very important to be a patient advocate because when you have a personal story, it resonates with people much more than just reading about something or hearing about something on a ballot.  It’s really vital for the future. Everybody has somebody or knows somebody who had macular degeneration or became visually impaired. If they don’t, they need to be educated about it.

Q: Tell us about your Radio Show.

My radio show “Second Vision” is about personal development and reinventing yourself and your life’s vision when the first one fails. It was the first internet radio show to support the blind and visually impaired, so that’s why I’m passionate about it. I’ve had scores of authors on there over the years who’ve written amazing books about how to better yourself and personal stories from people who have overcome adversity from all different types of challenges in terms of emotional health, physical health or problems in their lives. You can find anything on the Second Vision website from interviews on Reiki and meditation to Erik Weihenmayer, the blind man who climbed the seven summits (the highest mountains of each of the seven continents).

Q: Why is stem cell research important?

I do think that stem cells will help people with blindness. I don’t know whether it will be a 100% treatment. Scientists may have to do something else along the way to perfect stem cell treatments whether it’s gene therapy or changing the number of cells or types of cells they inject into the eye. I really do have a huge amount of faith in stem cells. If they can regenerate other parts of the body, I think the eye will be no different.

To read more about Kristin Macdonald and her quest for a Second Vision, please visit her website.


Related Links:

Another way to dial back stem cell hype (but not hope): Put a dollar figure on it

In an effort to reign in the hype surrounding stem cell research that has led to a proliferation of unapproved and potentially dangerous stem cell therapies, the International Society for Stem Cell Research (ISSCR) recently released updated guidelines outlining conduct for stem cell researchers that,  for the first time, included communications activities.  At only 1.5 pages in the 37-page document, the statements around communications asked researchers, communications professionals, institutions and the media to be more proactive in combatting stem cell hype by ensuring accuracy and balance in communications activities.

Stock Image

Stock Image

It’s too early to know what the full impact of the guidelines will be, however, the communications recommendations did generate a good deal of interest and some media, at least, have taken steps to address the issue.

Whether directly influenced by the guidelines or not, in the final plenary session of the ISSCR annual meeting last week, Professor Roger Barker, a research-clinician at the University of Cambridge, provided a candid portrayal of some of the challenges of preclinical and early clinical research.

Though he may have poked a small hole in some of the optimism that characterized the four-day conference, in providing a rare glimpse of the real costs of research, Dr. Barker might also have given us a new way to frame research to downplay hype.

Dr. Roger Barker

Dr. Roger Barker

Dr. Barker is one of many researchers across the globe working on a potential cell-based treatment for Parkinson’s Disease. Parkinson’s is a rather straightforward disease to tackle in this way, because its cause is known: the death of cells that produce the chemical dopamine. Even so, the challenges in developing a treatment are many. Apart from the design of a clinical study (which includes, for example, careful selection of the Parkinson’s patients to include; as Barker pointed out, there are two main types of Parkinson progression and one type may respond to a treatment while the other may not. This is a real concern for Barker, who commented that “a lack of rigour in selecting patients has dogged the field for the past 25 years.”), there are several other factors that need to be addressed in the pre-clinical work, such as identifying the best type of cells to use, how to scale them up and make them both GMP-compliant and standardized for reproducibility.

Such work, Barker estimated, costs between £2 and £3 million (or roughly $3-5 million, valued at pre-Brexit currency rates, one would assume). And, having invested so much to this point, you don’t even have something that can be published yet.

Running the actual clinical phase 1 study, with roughly 20 patients, will cost millions more. If it doesn’t work, you’re back to lab and in search of more pre-clinical funding.

But, assuming the study nets the desired results, it’s still only looking at safety, not efficacy. Getting it to phases 2 and 3 costs several orders of magnitude more. Put in this light, the $3 billion USD given to the California Institute for Regenerative Medicine seems like not nearly enough. The Ontario Institute for Regenerative Medicine’s $25 million CAD is nothing at all. Not that we aren’t grateful — we do what we can to maximize impact and make even a small investment worthwhile. Every step counts.

Another point to consider is whether the final therapy will be more cost-effective than existing, approved medical interventions. If it’s not, there is little incentive in pursuing it. This is the notion of headroom that I’ve heard discussed more directly at commercialization-based conferences (and is very well explained here) but is one that will become increasingly relevant to research as more basic and translational work finds its way into the clinic.

Talking about money with regard to health can be seen as tedious and even crass. The three short talks given by patient advocates at the ISSCR meeting served to emphasize this – each outlined personal tragedy connected to illness or disease: congestive heart failure at 11 years of age, four generations of a family with sickle cell disease, retinitis pigmentosa that derailed a young woman’s budding career. You simply can’t put a price on a person’s life, happiness and well-being. Each of these patients, and millions more, have hope that research will find an answer. It’s a lofty goal, one that is sometimes hard to remember in the lab trenches when a grant doesn’t materialize or a negative result sends the work back to ground zero.

And therein lies some of the tension that can easily lead to hype. We do want to fly high. We do want to deliver cures and therapies. We need to be reminded, by interactions with the patient community, of what’s at stake and what we can gain for humanity. The field should and will continue to strive to achieve these goals.

But not without responsibility. And a dose of realism.


This post appears simultaneously on OIRM Expression and appears here with permission by the author Lisa Willemse.

Presentations at ISSCR that caught our eye: Stem cell clinical trials expand as work to improve our understanding of just how they work goes on in parallel

In a special edition of our weekly roundup, here are some highlights from just the first two days of the four-day annual meeting of the International Society for Stem Cell Research

 Seeing stem cells from both sides now. As the biggest gathering of stem cell researchers each year, the annual meeting of the International Society for Stem Cell Research offers a chance to catch up on progress across the complete spectrum of research, from fundamental exploration in the lab to clinical trials. This year’s meeting in San Francisco offers more advances toward the clinic than ever before, but it also shows a cadre of basic researchers struggling to understand what is really going on at the genetic and molecular level with some of the biggest breakthroughs of the past few years. It is a bit like the opening verse of Joni Mitchell’s song “Both Sides Now” in which she laments that even after seeing clouds as beautiful patterns and as blocks to the sun she does not really know clouds at all.

Yamanaka at ISSCR 2016

Nobelist Shinya Yamanaka at the annual ISSCR meeting

Nothing captured that spirit better than the opening talk on the second day by Nobel Prize winner Shinya Yamanaka who maintains labs at Kyoto University in Japan and at the Gladstone institutes here in San Francisco, about a mile from the site of the meeting. This year marks the 10th anniversary of his Nobel-winning discovery that you can use genetic factors to reprogram adult cells into embryonic-like stem cells called iPS cells. Even as his institute is supplying the cells for the first ever clinical trial using iPS, in this case in the blinding disease called macular degeneration, he spent much of his talk discussing his ongoing basic research trying to understand what really goes on in that reprogramming process, and why so many cells are refractory to reprogramming with only a few percent in most experiments becoming stem cells.

Before launching into his ongoing basic research—some of it from a research thread he began to unravel as a postdoc at the Gladstone—he told an enlightening tale of how he had been reprogrammed as a scientist.  He said that he went from a a basic researcher just working in his lab to someone who spent much of their time talking to government officials, bankers and donors. But he noted that like our cells, part of him was refractory to reprogramming and he still liked getting into the lab to do the basic research needed to understand the creation of iPS cells and make it it faster and more efficient, which is critical to any future role for the cells at the other end of the research pipeline—treating patients in need.

 

It takes a neighborhood. As usual much of the basic science revolved around the lab recipes needed to keep stem cells in the stem cell state in the lab, or how to efficiently direct them to become a specific type of adult tissue. On the latter there was also considerable work presented on how to get around the fact that too often the adult cells created from stem cells are not fully mature and function more like those tissues would in the fetus than they should in an adult patient.

Fiona Watt of Kings College London presented her work on studying the one “organ” that is easier to study in humans than mice: the skin hair follicle. In the furry critters the hair follicles are too close together to easily isolate individual ones. With our sparser covering it is easy to study single hair follicles, which serve as the niche that houses skin stem cells until they are needed to replenish or repair our outer barrier. In recent years, when trying to understand how stem cells stay stem cells or decide to mature into specific tissue, researchers have increasingly turned their attention to the niches all over the body that stem cells call home. They are finding that there are many facets to these homes—physical, chemical and genetic—that like any neighborhood, impact how a stem cell grows up.

Watt opened by paying tribute to a pioneer in the field who died this past year, Harvard Med School’s Howard Green, who was always a treat to interview when I was there, and who pioneered single cell analysis in skin four decades ago. Watt’s work tries to break down the various components of the skin stem cell niche in the lab to see how each contributes to cell fate. She looked at the extracellular matrix, the scaffold that holds cells in place, and found a link between the size of the hole in the scaffold and cells remaining stem cells. She also found difference between soft and hard scaffolds. She noted other factors such as the type of cell that lives next door and the oxygen level all impact the cell decisions.

She suggested that these determinants of cell fate are likely consistent across stem cell niches throughout the body and will be critical to more efficiently producing replacement tissues to help patients.

 

Jumping from A to C, skipping B.  Two researchers followed Watt who are trying to develop ways to skip the step of turning adult cells in to iPS-type stem cells and instead convert them directly into the desired tissue needed for repair. Stanford’s Marius Wernig, who cited funding from CIRM and the New York Stem Cell Foundation, reported on his work trying to improve his breakthrough from a few years ago in which he converted skin into nerve with just one genetic factor. He is investigating the underlying structures of our DNA to try to understand why only 20 percent of cells make the desired conversion. He is finding some answers but has more to ferret out.

 

parmar

Malin Parmar

Then Malin Parmar of Sweden’s Lund University went into more detail on the fetal cell and stem cell transplant trials she is working with in Parkinson’s disease that she described at our public symposium earlier in the week. But she closed with work that she thinks could be the ultimate best solution to the disease.  Finding genetic factors that can convert other nerve cells directly into the dopamine-producing nerve cells lost in patients with the disease. She started with Wernig’s recipe and added a genetic factor known to drive cells to become dopamine nerves. She succeeded in turning brain cells called glial cells into dopamine nerves inside the brains of mice and showed they made the needed connections to other brain cells. But the work is still some years from getting to patients.

 

The complexities of the heart.  Yesterday afternoon five researchers presented different ways to figure out how to use stem cells to repair or replace a very complex organ, the heart. Shen Ding from Gladstone, who has pioneered the concept of using chemical instead of genetic factors to reprogram cells, presented his latest work in which he used that technique to grow partially mature heart cells in the lab, transplanted them into mice and saw them mature into tissue that improved heart function in a model of heart attack. He said his next experiments will involve finding a way to deliver the chemicals directly into the damaged heart to try to get the reprogramming done in the living animal.

57966-heartinribcagesmall

Stephanie Protze, of the McEwen Centre for Regenerative Medicine in Toronto, presented work on another component of the heart, the pace maker cells that ensure any new muscle cell beats at the right speed.  She described a recipe to drive stem cells to become pace maker cells, but there was a glitch. They beat at 150 beats per minute, which is the fetal rate not the adult rate. So, once again the field ran into the block of creating only partially mature tissue.

Tamer Mohamed, also of the Gladstone, presented work using chemicals to convert heart scar tissue to functional heart muscle. His work tweaked an earlier recipe that resulted in fewer than one percent of cells converting to a procedure that resulted in 30 percent. In the mouse model he saw improved heart function and reduced scarring.

University of Pittsburgh’s Lei Yang presented work on a very big, long-term goal for the field: producing a complete replacement heart. Like several other teams, his group started with a mouse donor heart and used detergents to wash away the cells so that all that was left was the scaffold of that extracellular matrix mentioned above.  He then seeded the scaffold with heart cells derived from iPS cells and let them mature.  The work resulted in what he called “beating heart constructs.”  Some of the cells beat with needed synchronicity and some did not.

All in all, the meeting exudes measured confidence. The field is clearly making rapid strides toward understanding stem cells well enough to create meaningful therapies.  However, it is ripe for what is called “reverse translation,” which is taking the findings of early clinical trials  that don’t perform quite as well as desired, and going back to  the lab to figure out how to make them better.

Circular RNAs: the Mind-Boggling Dark Matter of the Human Genome

We were just a few hours into the 2016 annual meeting of the International Society for Stem Cell Research (ISSCR) yesterday afternoon and my mind was already blown away. Pier Paolo Pandolfi of the Beth Israel Deaconess Medical Center at Harvard, spoke during the first plenary session about circular RNAs, which he dubbed, “the mind-boggling dark matter of the human genome” because their existence wasn’t confirmed until just four years ago.

To introduce the topic, Pandolfi compared human DNA to that of bacteria. Both species contain stretches of DNA sequence called genes that contain the instructions for making proteins which collectively form our bodies. Each gene is first transcribed into messenger RNA (mRNA) which in turn is translated into a protein.

Iceberg

Our DNA contains 20,000 genes. But that genetic material is just the tip of the iceberg.

But with the ability to sequence all the mRNA transcripts of an organism, or its transcriptome, came a startling fact about how differently our genetic structure is organized compared to bacteria. It turns out that 88% of DNA sequence in bacteria make up genes that code for proteins but only 2% of human DNA sequence directly codes for proteins. So what’s going with the other 98%? Scientist typically call this 98% chunk of the genome “regulatory DNA” because it contains sequences that act as control switches for turning genes on or off. But Pandolfi explained that more recent studies suggest that a whopping 70% of our genome (maybe even 95%) is transcribed into RNA but those RNA molecules just don’t get translated into protein.

 

One type of this “non-coding” RNA which we’ve blogged about plenty of times is called microRNA (miRNA). So far, about 5,000 human miRNAs have been identified compared to the 20,000 messenger RNAs that code for proteins. But by far the most abundant non-coding RNA in our transcriptome is the mysterious circular RNA (circRNA) with at least 100,000 different transcripts. circRNA was first observed as cellular structures in the 1980’s via electronic microscope images. Then in the 1990’s a scientist published DNA sequencing data suggesting the existence of circRNA. But the science community at that time panned the results, discrediting it as merely background noise of the experiments.

Pandolfi_2

Pier Paolo Pandolfi
Image: Beth Israel Deaconess Medical Center

But four years ago, the circRNAs were directly sequenced and their existence confirmed. The circRNAs are formed when messenger RNA goes through a well-described trimming process of its sequence. Some of the excised pieces of RNA form into the circular RNAs. It would seem that these circRNAs are just throw away debris but Pandolfi’s lab has found evidence that they directly play a role in cellular functions and even cancer.

His team studies a gene called Pokemon which, when genetically “knocked out” or removed from a mouse’s genome, leads to cancer. Now, it turns out this knockout not only removes the Pokemon protein but also a Pokemon circRNA (circPok). When the lab added back just the Pokemon gene, as you might expect, it acted to suppress cancer in the mice. But when just the circPok was added back, stunningly, it increased the formation of cancer in the mice. Given that genetic knockouts are one of the most pervasive techniques in biomedical science, a closer look at circRNAs that may have been overlooked in all of those results is clearly warranted.

Though this finding is somewhat scary in the fact that it’s a whole aspect of our genome that we’ve been unaware of, one fortunate aspect of circRNA is that they all carry a particular sequence which could be used as a target for a new class of drugs.

This data may extend to stem cells as well. We know that microRNAs have critical roles in regulating the maturation of stem cells into specialized cell types. Since circRNAs are thought to act by competing microRNA, it may not be long before we learn about circRNA’s role in stem cell function.

The other speakers at the first plenary session of the ISSCR annual meeting all gave high caliber talks. Luckily, Paul Knoepfler live blogged on two of those presentations. Here are the links:

 

Multi-Talented Stem Cells: The Many Ways to Use Them in the Clinic

CIRM kicked off the 2016 International Society for Stem Cell Research (ISSCR) Conference in San Francisco with a public stem cell event yesterday that brought scientists, patients, patient advocates and members of the general public together to discuss the many ways stem cells are being used in the clinic to develop treatments for patients with unmet medical needs.

Bruce Conklin, Gladstone Institutes & UCSF

Bruce Conklin, Gladstone Institutes & UCSF

Bruce Conklin, an Investigator at the Gladstone Institutes and UCSF Professor, moderated the panel of four scientists and three patient advocates. He immediately captured the audience’s attention by showing a stunning video of human heart cells, beating in synchrony in a petri dish. Conklin explained that scientists now have the skills and technology to generate human stem cell models of cardiomyopathy (heart disease) and many other diseases in a dish.

Conklin went on to highlight four main ways that stem cells are contributing to human therapy. First is using stem cells to model diseases whose causes are still largely unknown (like with Parkinson’s disease). Second, genome editing of stem cells is a new technology that has the potential to offer cures to patients with genetic disorders like sickle cell anemia. Third, stem cells are known to secrete healing factors, and transplanting them into humans could be beneficial. Lastly, stem cells can be engineered to attack cancer cells and overcome cancer’s normal way of evading the immune system.

Before introducing the other panelists, Conklin made the final point that stem cell models are powerful because scientists can use them to screen and develop new drugs for diseases that have no treatments or cures. His lab is already working on identifying new drugs for heart disease using human induced pluripotent stem cells derived from patients with cardiomyopathy.

Scientists and Patient Advocates Speak Out

Malin Parmar, Lund University

Malin Parmar, Lund University

The first scientist to speak was Malin Parmar, a Professor at Lund University. She discussed the history of stem cell development for clinical trials in Parkinson’s disease (PD). Her team is launching the first in-human trial for Parkinson’s using cells derived from human pluripotent stem cells in 2016. After Parmar’s talk, John Lipp, a PD patient advocate. He explained that while he might look normal standing in front of the crowd, his PD symptoms vary wildly throughout the day and make it hard for him to live a normal life. He believes in the work that scientists like Parmar are doing and confidently said, “In my lifetime, we will find a stem cell cure for Parkinson’s disease.”

Adrienne Shapiro, Patient Advocate

Adrienne Shapiro, Patient Advocate

The next scientist to speak was UCLA Professor Donald Kohn. He discussed his lab’s latest efforts to develop stem cell treatments for different blood disorder diseases. His team is using gene therapy to modify blood stem cells in bone marrow to treat and cure babies with SCID, also known as “bubble-boy disease”. Kohn also mentioned their work in sickle cell disease (SCD) and in chronic granulomatous disease, both of which are now in CIRM-funded clinical trials. He was followed by Adrienne Shapiro, a patient advocate and mother of a child with SCD. Adrienne gave a passionate and moving speech about her family history of SCD and her battle to help find a cure for her daughter. She said “nobody plans to be a patient advocate. It is a calling born of necessity and pain. I just wanted my daughter to outlive me.”

Henry Klassen (UC Irvine)

Henry Klassen, UC Irvine

Henry Klassen, a professor at UC Irvine, next spoke about blinding eye diseases, specifically retinitis pigmentosa (RP). This disease damages the photo receptors in the back of the eye and eventually causes blindness. There is no cure for RP, but Klassen and his team are testing the safety of transplanting human retinal progenitor cells in to the eyes of RP patients in a CIRM-funded Phase 1/2 clinical trial.

Kristen MacDonald, RP patient

Kristen MacDonald, RP patient

RP patient, Kristen MacDonald, was the trial’s first patient to be treated. She bravely spoke about her experience with losing her vision. She didn’t realize she was going blind until she had a series of accidents that left her with two broken arms. She had to reinvent herself both physically and emotionally, but now has hope that she might see again after participating in this clinical trial. She said that after the transplant she can now finally see light in her bad eye and her hope is that in her lifetime she can say, “One day, people used to go blind.”

Lastly, Catriona Jamieson, a professor and Alpha Stem Cell Clinic director at UCSD, discussed how she is trying to develop new treatments for blood cancers by eradicating cancer stem cells. Her team is conducting a Phase 1 CIRM-funded clinical trial that’s testing the safety of an antibody drug called Cirmtuzumab in patients with chronic lymphocytic leukemia (CLL).

Scientists and Patients need to work together

Don Kohn, Catriona Jamieson, Malin Parmar

Don Kohn, Catriona Jamieson, Malin Parmar

At the end of the night, the scientists and patient advocates took the stage to answer questions from the audience. A patient advocate in the audience asked, “How can we help scientists develop treatments for patients more quickly?”

The scientists responded that stem cell research needs more funding and that agencies like CIRM are making this possible. However, we need to keep the momentum going and to do that both the physicians, scientists and patient advocates need to work together to advocate for more support. The patient advocates in the panel couldn’t have agreed more and voiced their enthusiasm for working together with scientists and clinicians to make their hopes for cures a reality.

The CIRM public event was a huge success and brought in more than 150 people, many of whom stayed after the event to ask the panelists more questions. It was a great kick off for the ISSCR conference, which starts today. For coverage, you can follow the Stem Cellar Blog for updates on interesting stem cell stories that catch our eye.

CIRM Public Stem Cell Event

CIRM Public Stem Cell Event

Free public event will detail the many ways stem cells are used in clinical trials today

The hundreds of active stem cell clinical trials being run in the US, and indeed around the world, provide ample evidence that our favorite cells are truly multi-talented. There are so many different ways researchers are using them to develop therapies we would be hard-pressed to name them all. However, most fall into five general categories that will be discussed at a free public symposium CIRM is co-hosting in conjunction with the International Society for Stem Cell Research during its annual meeting in San Francisco.

Moscone at dusk

San Francisco’s Moscone Center is close to BART and Muni public transit

The free public event will run from 6:00 to 7:30 on Tuesday evening June 21 at the Moscone West convention center, room 2009, on the corner of Howard and Fourth streets in San Francisco. After a brief overview, four researchers will describe active clinical trials and how stem cells provide hope for therapies in different diseases.  The last half hour will be open for general questions from the audience.

All the details are at a special page on EventBright where you can register to attend. The evening will start with Bruce Conklin of the Gladstone Institutes providing an overview of the many ways to use stem cells, including his own work using them to create laboratory models of heart disease. Then:

  • Malin Parmar of Sweden’s Lund University will discuss a Parkinson’s disease trial where stem cells are used to replace vital brain cells destroyed by the disease;
  • Donald Kohn of the University of California, Los Angeles, will provide details of two trials that combine stem cells and gene therapy, one for sickle cell anemia and one for severe combined immune deficiency, also called Bubble Baby disease;
  • Henry Klassen of University of California, Irvine, will talk about using progenitor stem cells to deliver factors that can protect the photoreceptors in the eyes of patients who have a blinding condition;
  • Catriona Jamieson of the University of California, San Diego will describe the bad boy of the stem cell world, the cancer stem cell, and clinical trials she is conducting to attack those cells.

While some of the hundreds of current stem cell clinical trials will not produce the desired impact on their target diseases, they will all make strides toward learning how to optimize the great potential of stem cell therapies.

Right now CIRM is funding 16 different clinical trials in diseases as varied as HIV/AIDS and type 1 diabetes. Over the next 5 years we hope to add another 50 clinical trials to that list. The field of regenerative medicine is advancing. This event is a chance for you to understand the progress, and the challenges, that we face in bringing potentially life-changing, even life-saving therapies to the people who need it the most, the patients.

Up your “bump-rate” at the biggest stem cell meeting of the year

Often times great science develops after two researchers bump into each other and trade ideas. When I worked at Harvard we designed a new research building with two-story kitchens on every-other floor to force researchers from one floor to bump into researchers from the neighboring floor. Over the next few years I documented several collaborations between those neighbors.

ISSCR 1

If you really want to increase your bump rate there is no better place than a scientific meeting, and in the stem cell field, there is no better meeting than the annual meeting (link) of the International Society for Stem Cell Research (ISSCR). This year’s session expects to bring more than 4,000 stem cell researchers at all stages of the research pipeline to San Francisco June 21st-25th. Full disclosure: CIRM is co-sponsoring the meeting this year.

 Something for the lay public, too. Not a researcher? There’s something for the general lay public as well. On Tuesday evening June 21st, CIRM will co-host with ISSCR an hour and a half discussion with five stem cell scientists covering heart disease, cancer, blindness, sickle cell anemia and Parkinson’s disease. You can find more information and register for the 6:00-7:30 pm event here.

Researcher still have time to apply to speak.

 The ISSCR wants to capture the best science in real time, so they have a system that allows you to submit abstracts for research you have recently completed.  If one of your experiments has just produced some exciting data, you can submit it here through May 2. And discount advance registration ends May 4.

Even if you don’t present, you will have the chance to choose between nearly 200 oral presentations and 1,400 poster presentations. The meeting also offers a career fair with organizations looking to hire, meet-up hubs and an orientation for new attendees. All are chances to increase your bump rate and the likelihood the meeting will result in your research taking a new and exciting trajectory.

And of course, don’t’ underestimate the bump rate in the hallways of the meeting and in the coffee shops and bars surrounding the convention center. Bend an elbow for science.

If you need a bit of a financial hand to get to the meeting, STEMCELL Technologies is having a drawing through ISSCR for four $500 travel awards to offset costs of getting to the meeting.

For a sampling of the exciting science presented at prior ISSCR annual meetings you can scan our blog posts for real-time coverage from the meetings in Boston and Vancouver.

ISSCR 2014: Tony Atala, Jason Burdick and the Power of Tissue Engineering

The progress in tissue engineering in just the past two decades has been like the construction industry moving from simple lean-to structures to homes with plumbing, heating and cooling systems. We are not yet ready to build a high-rise—think of a beating functioning heart—but we are making major strides toward that goal.

One of the founders of the field, Wake Forest’s Dr. Tony Atala, led off this morning plenary session at the annual meeting of the International Society for Stem Cell Research. He started trying to build simple organs in 1990. His talk nicely mapped his progress through four levels of complexity of structure.

Tony Atala speaks about tissue engineering in a 2011 TED talk (credit: Wikipedia)

Tony Atala speaks about tissue engineering in a 2011 TED talk (credit: Wikipedia)

The first level, accomplished by a few teams, was our largest organ, skin, which is relatively simple because it is flat. Next, came simple hollow organs like blood vessels and the urethra that carries urine from the bladder. He followed that with more complex hollow organs, first the bladder and more recently the vagina. Last up were complex solid organs: the heart and the penis. He expects to begin clinical trials with the latter soon, which is eagerly anticipated by our military dealing with the aftermath IED explosive injuries from the wars in Iraq and Afghanistan.

He noted that researchers in the field quickly learned that just throwing cells on scaffolds and hoping they knew what to do was not enough in most cases. They need to grow blood vessels so they can get nourishment and communicate with their surroundings and they often have to make multiple cell types. His own work here benefited from a bit of geographic serendipity. His lab at the time was on the same floor as Judah Folkman’s at Harvard affiliated Children’s Hospital. Folkman is the father of the field of angiogenesis, the art of growing blood vessels.

Atala showed slides comparing injecting cells where you need new muscle, to cells plus scaffold, and finally to the two combined with a vessel growth factor. The three-way combo far outperformed the others. He published his first study using this technique for a hollow simple organ, the urethra, in 2011. At that point his patients had been living with the functional new organ for six years. They work and last.

Researchers almost always place a cell-scaffold complex in a soup of nutrients and growth factors called a bioreactor before implanting it. But at the time of implant, the organ is not mature. Atala said the body acts like a “finishing bioreactor” to fill out and strengthen the organ, which becomes fully mature around six months after implant. He showed images of this in-body growth in his first patients who had been born without a complete vagina and were given a fully functioning organ. He just published that study two months ago, eight years after the implants in order to make sure they stayed functional over time.

He then showed his animal model work creating a penis in rabbits. Being a highly vascular organ it required much more structure. He used a donor organ that had all its cells chemically washed away to leave just the intracellular scaffold. This structure helped guide the blood vessel growth and the rabbits succeeded in mating and having offspring.

His lab has begun early stage work for both liver and heart. They have created miniature livers about the size of a half dollar that are able to produce the appropriate proteins and metabolize drugs. They have used a 3-D printer to build two chambers of a heart that are able to beat in a dish, but their structure has not been stable. So, he noted much more work lies ahead for complex organs.

The second speaker, Jason Burdick from the University of Pennsylvania, concentrated on making better scaffolds for the stem cells, which can have three enhanced properties:

  1. they can be instructive, they can tell cells what to do;
  2. they can be dynamic, they can react to their environment and the cells around them;
  3. they can lead to heterogeneity, they can provide varied instructions so you get the different cell types that you need for a complex tissue.

He discussed two examples, the first was growing better cartilage (as he joked, for injured World Cup soccer players). One problem with early gels used as scaffold was they held the cells individually apart from each other limiting their ability to communicate with each other. This cell-to-cell cross talk is key to tissue maturation. He showed how you could chemically alter the gel to enhance this communication. He also showed how you could implant the gels with microspheres loaded with growth factors to deliver instructions to the cells.

Burdick’s second example focused on minimizing injury after an induced heart attack in rodents. But instead of loading the gel with cells, they loaded it with microspheres that release chemicals that summons the stem cells waiting quietly in reservoirs in all of us. They saw sustained release of the chemicals for 21 days and significant improvement in heart function.

But he closed with a fun twist. The first heart experiment used a strict time-release formulation. He said it would be much better if the chemicals were released at the points the heart needs it the most. So, he is working on a system that releases the chemical based on the levels of an enzyme the heart makes when it is injured. He is hoping this right-amount-at-the-right-time formula will be even better.

We have a short video of the highlights of a workshop we held on tissue engineering that you can watch to get a better feel for where the field is going.

Don Gibbons

ISSCR 2014: Lorenz Studer talks Parkinson’s cells

Two presentations at the International Society for Stem Cell (ISSCR) conference, from two different sides of the pond, looked at ways to get stem cell therapies out of the lab and into patients. They both focused on the problems that need to be overcome, but came to the positive conclusion that this could be done.

Lorenz Studer, from the Sloan Kettering Institute for Cancer Research, has been working since 1995 to try and find a renewable source of cells to treat Parkinson’s Disease. He thinks he’s finally found it.

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Let’s back up a little. Studer says the key movement problems seen in people with Parkinson’s (tremors, rigidity, difficulty moving) are caused by a loss of the dopamine-producing neurons in their brain. The good news is that this creates a great target for researchers to try and find a replacement. The bad news is it’s devilishly difficult producing the right kind of cell to survive and function in the brain.

In the 1980s fetal tissue transplants were tried to treat the disease and while these tissues seemed to engraft into the brain and have survived, in some cases, for more than 30 years, they only benefitted a small number of patients and had some unexpected side effects in others. So Studer focused his approach using dopamine-producing neurons (the kind that are destroyed by Parkinson’s disease) that derived from human embryonic stem cells (hESC).

He found that these hESC dopamine neurons worked well in animal models, surviving term and mirroring the normal development of a human neuron.

Studer says new MRI technology means we can be much more precise in where we place these cells in the brain, ensuring that they go exactly where we want them.

So Studer feels he has the right cells in the right number and the ability to place them in the right location. But that still left a number of questions: how do we know they are engrafting into the brain and producing dopamine, and is that producing any impact on behavior?

Studer turned to optogenetics, the use of light to control neurons, to assess and measure what was happening in the brain with these transplanted cells. He put markers into the neurons that were being transplanted and then used pulses of light to switch them on and off. Turning the cells off stopped the dopamine production; turning them back on increased it. They found that the cells were indeed functioning and producing the dopamine.

That still left the question of whether that actually changed behavior. So he devised a study comparing mice with healthy brains to those with Parkinson’s-like lesions on one side of the brain. He put the mice in a tunnel with food pellets on either side of it. The mice with a healthy brain went along the tunnel and ate food from both sides. The other mice ate food almost completely from just one side: the side opposite where the lesion in their brain was.

Then Studer transplanted the dopamine-producing neurons into the study mice and repeated the experiment. This time they ate from both sides of the tunnel suggesting the transplanted cells were producing dopamine, affecting behavior in a positive way.

He hopes to be in clinical trails in patients in late 2016 or early 2017.

For Roger Barker of the University of Cambridge, UK, finding the right cells was only one of four basic questions that need to be considered when trying to take stem cell therapies into clinical trials:

  1. What is the evidence that cell therapies work in replacement
  2. Can you make an authentic, effective cell replacement
  3. How can you test such therapies in patients
  4. Are these competitive to existing therapies

Question 1
Baker says numerous studies in animals over the years have shown that using dopamine-producing stem cells to replace the damaged cells can increase dopamine levels.

A European contingent called TransEuro is about to start a clinical trial to see if this also works well in people. This consortium is using fetal tissue and will treat patients with more early stage disease when, at least in theory, it’s more likely to respond to the therapy. They hope to transplant their first patient in the next four weeks.

Question 2
Can you make an authentic dopamine producing neuron? Baker said Studer’s work suggests you can, as long as it is a form of the cell called an A9 NIGRAL dopaminergic neuron. Barker says even these cells are not perfect cells but they have enough qualities to suggest they are worth trying.

Question 3
Barker says many therapies have been tested in early stage clinical trials in the past that, based on preclinical evidence, weren’t good candidates. When they failed they set the field back by creating the impression that stem cells wouldn’t work for this kind of approach when the real lesson is that stem cells may well work, but they have to be the right ones, used in the right way.

He says GFORCE—a consortium featuring CIRM, and groups in New York, the UK and Japan—is now working as a group to set common standards and agreed upon best practices, so future trials can be compared to each other rather than stand alone.

Here at the stem cell agency we have also created a Regenerative Medicine Consortium to bring together leading companies, academic and funding institutions to share best practices and resources, and to help speed up this process and make it more consistent and efficient.

Question 4
Many existing therapies today work very well in helping control some of the symptoms, at least in the early stages. To be effective these new stem cell therapies have to be at least as good—and at least as affordable—as existing treatments. Whether that proves to be the case will determine whether, even if they show they are effective, they become widely available.

Both scientists acknowledge we have come a long way in recent years. Both also acknowledge we still have a long way to go. But at least now we seem to all be asking the same questions and that is a clear sign of progress.

At the stem cell agency we have invested more than $43 million in 23 different research projects aimed at finding new treatments for Parkinson’s.
Kevin McCormack

ISSCR 2014: Talking Twitter and Stem Cells

One of the fascinating things about the ISSCR (International Society for Stem Cell Research) annual conference is that you learn so much about so many things, ranging from the latest in Parkinson’s research (more on that later this week) to the impact of social media on people’s knowledge about stem cells.

At a poster presentation Wednesday, Julie Robillard, Ph.D., a post doc researcher at the University of British Columbia in Vancouver, BC, talked about the way that people use Twitter to talk about stem cells.

Julie, a neuroscientist by training, became fascinated by the use of social media and has done a number of studies looking at the use of social media for topics like information about aging, gene therapy and now stem cells.

Dr. Julie Robillard at ISSCR 2014.

Dr. Julie Robillard at ISSCR 2014.

She says social media is reshaping how conversations take place between people who are interested in stem cells: anyone from a scientist to a patient to a provider of sham therapies. She says there is a lot of information out there about stem cells but the quality is not always great and in some cases it’s downright questionable.

For her poster presentation, entitled Stem Cells in Social Media: Implications for Public Policy, Julie focused on Twitter and searched for key words such as “stem cell” and “spinal cord injury.”

She said the thing that surprised her most was the sheer diversity of people that were using Twitter to communicate about stem cells: people from 41 different countries with the US, Canada, the UK and Australia the top four. She says this is clear evidence there is worldwide interest in stem cell research. The problem, however, is that the quality of many of the tweets was also widely varied. Some came from researchers and were thoughtful and trying to raise awareness about new research or important questions, but others—many others—were more interested in promoting stem cells as cures for everything from sagging skin or acne to severed spinal cords.

Julie says 15 percent of tweets came from companies involved in stem cell research. In some cases they may be companies who have results about research they are doing, but in others it was to promote a product or treatment that wasn’t necessarily approved or proven. Julie says they’re quite clever about how they do it, using hashtags (i.e. #stemcells) that suggest it came from someone’s personal account rather than a business address, but they then link back to the company site.

News reports, stories in newspapers, on the radio and TV or online are the single biggest drivers of traffic on Twitter and are a reminder of the importance of good journalism when covering these issues. A poorly written or researched story that makes inflated claims about a treatment, or fails to mention that the research was done in mice not people, can get huge play on social media and mislead many people. This is a little worrying when fewer and fewer mainstream media outlets have a dedicated science journalist on staff.

Julie cautions that when you read a tweet and don’t know the person who sent it, it’s a case of buyer-beware, don’t just accept it at face value.

She also says it’s a reminder to those of us trying to inform the public about all the progress being made with stem cell research that we need to be more engaged and more active, so that our voices can help drown out those with bad information or shoddy products to sell.

Kevin McCormack