Stem cell stories that caught our eye: spinal cord injury trial update, blood stem cells in lungs, and using parsley for stem cell therapies

More good news on a CIRM-funded trial for spinal cord injury. The results are now in for Asterias Biotherapeutics’ Phase 1/2a clinical trial testing a stem cell-based therapy for patients with spinal cord injury. They reported earlier this week that six out of six patients treated with 10 million AST-OPC1 cells, which are a type of brain cell called oligodendrocyte progenitor cells, showed improvements in their motor function. Previously, they had announced that five of the six patients had shown improvement with the jury still out on the sixth because that patient was treated later in the trial.

 In a news release, Dr. Edward Wirth, the Chief Medical officer at Asterias, highlighted these new and exciting results:

 “We are excited to see the sixth and final patient in the AIS-A 10 million cell cohort show upper extremity motor function improvement at 3 months and further improvement at 6 months, especially because this particular patient’s hand and arm function had actually been deteriorating prior to receiving treatment with AST-OPC1. We are very encouraged by the meaningful improvements in the use of arms and hands seen in the SciStar study to date since such gains can increase a patient’s ability to function independently following complete cervical spinal cord injuries.”

Overall, the trial suggests that AST-OPC1 treatment has the potential to improve motor function in patients with severe spinal cord injury. So far, the therapy has proven to be safe and likely effective in improving some motor function in patients although control studies will be needed to confirm that the cells are responsible for this improvement. Asterias plans to test a higher dose of 20 million cells in AIS-A patients later this year and test the 10 million cell dose in AIS-B patients that a less severe form of spinal cord injury.

 Steve Cartt, CEO of Asterias commented on their future plans:

 “These results are quite encouraging, and suggest that there are meaningful improvements in the recovery of functional ability in patients treated with the 10 million cell dose of AST-OPC1 versus spontaneous recovery rates observed in a closely matched untreated patient population. We look forward to reporting additional efficacy and safety data for this cohort, as well as for the currently-enrolling AIS-A 20 million cell and AIS-B 10 million cell cohorts, later this year.”

Lungs aren’t just for respiration. Biology textbooks may be in need of some serious rewrites based on a UCSF study published this week in Nature. The research suggests that the lungs are a major source of blood stem cells and platelet production. The long prevailing view has been that the bone marrow was primarily responsible for those functions.

The new discovery was made possible by using special microscopy that allowed the scientists to view the activity of individual cells within the blood vessels of a living mouse lung (watch the fascinating UCSF video below). The mice used in the experiments were genetically engineered so that their platelet-producing cells glowed green under the microscope. Platelets – cell fragments that clump up and stop bleeding – were known to be produced to some extent by the lungs but the UCSF team was shocked by their observations: the lungs accounted for half of all platelet production in these mice.

Follow up experiments examined the movement of blood cells between the lung and bone marrow. In one experiment, the researchers transplanted healthy lungs from the green-glowing mice into a mouse strain that lacked adequate blood stem cell production in the bone marrow. After the transplant, microscopy showed that the green fluorescent cells from the donor lung traveled to the host’s bone marrow and gave rise to platelets and several other cells of the immune system. Senior author Mark Looney talked about the novelty of these results in a university press release:

Mark Looney, MD

“To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia [low platelet count].”

If this newfound role of the lung is shown to exist in humans, it may provide new therapeutic approaches to restoring platelet and blood stem cell production seen in various diseases. And it will give lung transplants surgeons pause to consider what effects immune cells inside the donor lung might have on organ rejection.

Add a little vanilla to this stem cell therapy. Typically, the only connection between plants and stem cell clinical trials are the flowers that are given to the patient by friends and family. But research published this week in the Advanced Healthcare Materials journal aims to use plant husks as part of the cell therapy itself.

Though we tend to focus on the poking and prodding of stem cells when discussing the development of new therapies, an equally important consideration is the use of three-dimensional scaffolds. Stem cells tend to grow better and stay healthier when grown on these structures compared to the flat two-dimensional surface of a petri dish. Various methods of building scaffolds are under development such as 3D printing and designing molds using materials that aren’t harmful to human tissue.

Human fibroblast cells growing on decellularized parsley.
Image: Gianluca Fontana/UW-Madison

But in the current study, scientists at the University of Wisconsin-Madison took a creative approach to building scaffolds: they used the husks of parsley, vanilla and orchid plants. The researchers figured that millions of years of evolution almost always leads to form and function that is much more stable and efficient than anything humans can create. Lead author Gianluca Fontana explained in a university press release how the characteristics of plants lend themselves well to this type of bioengineering:

Gianluca Fontana, PhD

“Nature provides us with a tremendous reservoir of structures in plants. You can pick the structure you want.”

The technique relies on removing all the cells of the plant, leaving behind its outer layer which is mostly made of cellulose, long chains of sugars that make up plant cell walls. The resulting hollow, tubular husks have similar shapes to those found in human intestines, lungs and the bladder.

The researchers showed that human stem cells not only attach and grow onto the plant scaffolds but also organize themselves in alignment with the structures’ patterns. The function of human tissues rely on an organized arrangement of cells so it’s possible these plant scaffolds could be part of a tissue replacement cell product. Senior author William Murphy also points out that the scaffolds are easily altered:

William Murphy, PhD

“They are quite pliable. They can be easily cut, fashioned, rolled or stacked to form a range of different sizes and shapes.”

And the fact these scaffolds are natural products that are cheap to manufacture makes this a project well worth watching.

Newest member of CIRM Board is a fan of horses, Star Trek and Harry Potter – oh, and she just happens to be a brilliant cancer researcher too.

malkas-linda

An addition to the family is always a cause for celebration, whether it be a new baby, a puppy, or, in our case, a new Board member. That’s why we are delighted to welcome City of Hope’s Linda Malkas, Ph.D., as the newest member of the CIRM Board.

Dr. Malkas has a number of titles including Professor of Molecular and Cellular Biology at Beckman Research Institute; Deputy Director of Basic Research, Comprehensive Cancer Center, City of Hope; and joint head of the Molecular Oncology Program at the Cancer Center.

Her research focus is cancer and she has a pretty impressive track record in the areas of human cell DNA replication/repair, cancer cell biomarker and therapeutic target discovery. As evidence of that, she discovered a molecule that can inhibit certain activities in cancerous cells and hopes to move that into clinical trials in the near future.

California Treasure John Chiang made the appointment saying Dr. Malkas is “extraordinarily well qualified” for the role. It’s hard to disagree. She has a pretty impressive resume:

  • She served for five years on a National Cancer Institute (NCI) subcommittee reviewing cancer center designations.
  • She has served as chair on several NCI study panels and recently took on an advisory role on drug approval policy with the Food and Drug Administration.
  • She has published more than 75 peer-reviewed articles
  • She sits on the editorial boards of several high profile medical journals.

In a news release Dr. Malkas says she’s honored to be chosen to be on the Board:

“The research and technologies developed through this agency has benefited the health of not only Californians but the nation and world itself. I am excited to see what the future holds for the work of this agency.”

With all this in her work life it’s hard to imagine she has time for a life outside of the lab, and yet she does. She has four horses that she loves to ride – not all at the same time we hope – a family, friends, dogs and cats she likes spending time with. And as if that wasn’t enough to make you want to get to know her, she’s a huge fan of Star Trek, vintage sci-fi movies and Harry Potter.

Now that’s what I call a well-rounded individual. We are delighted to have her join the CIRM Team and look forward to getting her views on who are the greater villains, Klingons or Death Eaters.

 

Don’t Be Afraid: High school stem cell researcher on inspiring girls to pursue STEM careers

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

Shannon Larsuel

Shannon Larsuel is a high school senior at Mayfield Senior School in Pasadena California. Last summer, she participated in Stanford’s CIRM SPARK high school internship program and did stem cell research in a lab that studies leukemia, a type of blood cancer. Shannon is passionate about helping people through research and medicine and wants to become a pediatric oncologist. She is also dedicated to inspiring young girls to pursue STEM (Science, Technology, Engineering, and Mathematics) careers through a group called the Stem Sisterhood.

I spoke with Shannon to learn more about her involvement in the Stem Sisterhood and her experience in the CIRM SPARK program. Her interview is below.


Q: What is the Stem Sisterhood and how did you get involved?

SL: The Stem Sisterhood is a blog. But for me, it’s more than a blog. It’s a collective of women and scientists that are working to inspire other young scientists who are girls to get involved in the STEM field. I think it’s a wonderful idea because girls are underrepresented in STEM fields, and I think that this needs to change.

I got involved in the Stem Sisterhood because my friend Bridget Garrity is the founder. This past summer when I was at Stanford, I saw that she was doing research at Caltech. I reconnected with her and we started talking about our summer experiences working in labs. Then she asked me if I wanted to be involved in the Stem Sisterhood and be one of the faces on her website. She took an archival photo of Albert Einstein with a group of other scientists that’s on display at Caltech and recreated it with a bunch of young women who were involved in the STEM field. So I said yes to being in the photo, and I’m also in the midst of writing a blog post about my experience at Stanford in the SPARK program.

Members of The Stem Sisterhood

Q: What does the Stem Sisterhood do?

SL: Members of the team go to elementary schools and girl scout troop events and speak about science and STEM to the young girls. The goal is to inspire them to become interested in science and to teach them about different aspects of science that maybe are not that well known.

The Stem Sisterhood is based in Los Angeles. The founder Bridget wants to expand the group, but so far, she has only done local events because she is a senior in high school. The Stem Sisterhood has an Instagram account in addition to their blog. The blog is really interesting and features interviews with women who are in science and STEM careers.

Q: How has the Stem Sisterhood impacted your life?

SL: It has inspired me to reach out to younger girls more about science. It’s something that I am passionate about, and I’d like to pursue a career in the medical field. This group has given me an outlet to share that passion with others and to hopefully change the face of the STEM world.

Q: How did you find out about the CIRM SPARK program?

SL: I knew I wanted to do a science program over the summer, but I wasn’t sure what type. I didn’t know if I wanted to do research or be in a hospital. I googled science programs for high school seniors, and I saw the one at Stanford University. It looked interesting and Stanford is obviously a great institution. Coming from LA, I was nervous that I wouldn’t be able to get in because the program had said it was mostly directed towards students living in the Bay Area. But I got in and I was thrilled. So that’s basically how I heard about it, because I googled and found it.

Q: What was your SPARK experience like?

SL: My program was incredible. I was a little bit nervous and scared going into it because I was the only high school student in my lab. As a high school junior going into senior year, I was worried about being the youngest, and I knew the least about the material that everyone in the lab was researching. But my fears were quickly put aside when I got to the lab. Everyone was kind and helpful, and they were always willing to answer my questions. Overall it was really amazing to have my first lab experience be at Stanford doing research that’s going to potentially change the world.

Shannon working in the lab at Stanford.

I was in a lab that was using stem cells to characterize a type of leukemia. The lab is hoping to study leukemia in vitro and in vivo and potentially create different treatments and cures from this research. It was so cool knowing that I was doing research that was potentially helping to save lives. I also learned how to work with stem cells which was really exciting. Stem cells are a new advancement in the science world, so being able to work with them was incredible to me. So many students will never have that opportunity, and being only 17 at the time, it was amazing that I was working with actual stem cells.

I also liked that the Stanford SPARK program allowed me to see other aspects of the medical world. We did outreach programs in the Stanford community and helped out at the blood drive where we recruited people for the bone marrow registry. I never really knew anything about the registry, but after learning about it, it really interested me. I actually signed up for it when I turned 18. We also met with patients and their families and heard their stories about how stem cell transplants changed their lives. That was so inspiring to me.

Going into the program, I was pretty sure I wanted to be a pediatric oncologist, but after the program, I knew for sure that’s what I wanted to do. I never thought about the research side of pediatric oncology, I only thought about the treatment of patients. So the SPARK program showed me what laboratory research is like, and now that’s something I want to incorporate into my career as a pediatric oncologist.

I learned so much in such a short time period. Through SPARK, I was also able to connect with so many incredible, inspired young people. The students in my program and I still have a group chat, and we text each other about college and what’s new with our lives. It’s nice knowing that there are so many great people out there who share my interests and who are going to change the world.

Stanford SPARK students.

Q: What was your favorite part of the SPARK program?

SL: Being in the lab every day was really incredible to me. It was my first research experience and I was in charge of a semi-independent project where I would do bacterial transformations on my own and run the gels. It was cool that I could do these experiments on my own. I also really loved the end of the summer poster session where all the students from the different SPARK programs came together to present their research. Being in the Stanford program, I only knew the Stanford students, but there were so many other awesome projects that the other SPARK students were doing. I really enjoyed being able to connect with those students as well and learn about their projects.

Q: Why do you want to pursue pediatric oncology?

SL: I’ve always been interested in the medical field but I’ve had a couple of experiences that really inspired me to become a doctor. My friend has a charity that raises money for Children’s Hospital Los Angeles. Every year, we deliver toys to the hospital. The first year I participated, we went to the hospital’s oncology unit and something about it stuck with me. There was one little boy who was getting his chemotherapy treatment. He was probably two years old and he really inspired to create more effective treatments for him and other children.

I also participated in the STEAM Inquiry program at my high school, where I spent two years reading tons of peer reviewed research on immunotherapy for pediatric cancer. Immunotherapy is something that really interests me. It makes sense that since cancer is usually caused by your body’s own mutations, we should be able to use the body’s immune system that normally regulates this to try and cure cancer. This program really inspired me to go into this field to learn more about how we can really tailor the immune system to fight cancer.

Q: What advice do you have for young girls interested in STEM.

SL: My advice is don’t be afraid. I think that sometimes girls are expected to be interested in less intellectual careers. This perception can strike fear into girls and make them think “I won’t be good enough. I’m not smart enough for this.” This kind of thinking is not good at all. So I would say don’t be afraid and be willing to put yourself out there. I know for me, sometimes it’s scary to try something and know you could fail. But that’s the best way to learn. Girls need to know that they are capable of doing anything and if they just try, they will be surprised with what they can do.

A stem cell clinical trial for blindness: watch Rosie’s story

Everything we do at CIRM is laser-focused on our mission: to accelerate stem cell treatments for patients with unmet medical needs. So, you might imagine what a thrill it is to meet the people who could be helped by the stem cell research we fund. People like Rosie Barrero who suffers from Retinitis Pigmentosa (RP), an inherited, incurable form of blindness, which she describes as “an impressionist painting in a foggy room”.

The CIRM team first met Rosie Barrero back in 2012 at one of our governing Board meetings. She and her husband, German, attended the meeting to advocate for a research grant application submitted by UC Irvine’s Henry Klassen. The research project aimed to bring a stem cell-based therapy for RP to clinical trials. The Board approved the project giving a glimmer of hope to Rosie and many others stricken with RP.

Now, that hope has become a reality in the form of a Food and Drug Administration (FDA)-approved clinical trial which Rosie participated in last year. Sponsored by jCyte, a company Klassen founded, the CIRM-funded trial is testing the safety and effectiveness of a non-surgical treatment for RP that involves injecting stem cells into the eye to help save or even restore the light-sensing cells in the back of the eye. The small trial has shown no negative side effects and a larger, follow-up trial, also funded by CIRM, is now recruiting patients.

Almost five years after her first visit, Rosie returned to the governing Board in February and sprinkled in some of her witty humor to describe her preliminary yet encouraging results.

“It has made a difference. I’m still afraid of public speaking but early on [before the clinical trial] it was much easier because I couldn’t see any of you. But, hello everybody! I can see you guys. I can see this room. I can see a lot of things.”

After the meeting, she sat down for an interview with the Stem Cellar team to talk about her RP story and her experience as a clinical trial participant. The three-minute video above is based on that interview. Watch it and be inspired!

Stem Cell Stories that Caught our Eye: stem cell insights into anorexia, Zika infection and bubble baby disease

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

Stem cell model identifies new culprit for anorexia.

Eating disorders like anorexia nervosa are often thought to be caused by psychological disturbances or societal pressure. However, research into the genes of anorexia patients suggests that what’s written in your DNA can be associated with an increased vulnerability to having this disorder. But identifying individual genes at fault for a disease this complex has remained mostly out of scientists’ reach, until now.

A CIRM-funded team from the UC San Diego (UCSD) School of Medicine reported this week that they’ve developed a stem cell-based model of anorexia and used it to identify a gene called TACR1, which they believe is associated with an increased likelihood of getting anorexia.

They took skin samples from female patients with anorexia and reprogrammed them into induced pluripotent stem cells (iPSCs). These stem cells contained the genetic information potentially responsible for causing their anorexia. The team matured these iPSCs into brain cells, called neurons, in a dish, and then studied what genes got activated. When they looked at the genes activated by anorexia neurons, they found that TACR1, a gene associated with psychiatric disorders, was switched on higher in anorexia neurons than in healthy neurons. These findings suggest that the TACR1 gene could be an identifier for this disease and a potential target for developing new treatments.

In a UCSD press release, Professor and author on the study, Alysson Muotri, said that they will follow up on their findings by studying stem cell lines derived from a larger group of patients.

Alysson Muotri UC San Diego

“But more to the point, this work helps make that possible. It’s a novel technological advance in the field of eating disorders, which impacts millions of people. These findings transform our ability to study how genetic variations alter brain molecular pathways and cellular networks to change risk of anorexia nervosa — and perhaps our ability to create new therapies.”

Anorexia is a disease that affects 1% of the global population and although therapy can be an effective treatment for some, many do not make a full recovery. Stem cell-based models could prove to be a new method for unlocking new clues into what causes anorexia and what can cure it.

Nature versus Zika, who will win?

Zika virus is no longer dominating the news headlines these days compared to 2015 when large outbreaks of the virus in the Southern hemisphere came to a head. However, the threat of Zika-induced birth defects, like microcephaly to pregnant women and their unborn children is no less real or serious two years later. There are still no effective vaccines or antiviral drugs that prevent Zika infection but scientists are working fast to meet this unmet need.

Speaking of which, scientists at UCLA think they might have a new weapon in the war against Zika. Back in 2013, they reported that a natural compound in the body called 25HC was effective at attacking viruses and prevented human cells from being infected by viruses like HIV, Ebola and Hepatitis C.

When the Zika outbreak hit, they thought that this compound could potentially be effective at preventing Zika infection as well. In their new study published in the journal Immunity, they tested a synthetic version of 25HC in animal and primate models, they found that it protected against infection. They also tested the compound on human brain organoids, or mini brains in a dish made from pluripotent stem cells. Brain organoids are typically susceptible to Zika infection, which causes substantial cell damage, but this was prevented by treatment with 25HC.

Left to right: (1) Zika virus (green) infects and destroys the formation of neurons (pink) in human stem cell-derived brain organoids.  (2) 25HC blocks Zika infection and preserves neuron formation in the organoids. (3) Reduced brain size and structure in a Zika-infected mouse brain. (4) 25HC preserves mouse brain size and structure. Image courtesy of UCLA Stem Cell.

A UCLA news release summarized the impact that this research could have on the prevention of Zika infection,

“The new research highlights the potential use of 25HC to combat Zika virus infection and prevent its devastating outcomes, such as microcephaly. The research team will further study whether 25HC can be modified to be even more effective against Zika and other mosquito-borne viruses.”

Harnessing a naturally made weapon already found in the human body to fight Zika could be an alternative strategy to preventing Zika infection.

Gene therapy in stem cells gives hope to bubble-babies.

Last week, an inspiring and touching story was reported by Erin Allday in the San Francisco Chronicle. She featured Ja’Ceon Golden, a young baby not even 6 months old, who was born into a life of isolation because he lacked a properly functioning immune system. Ja’Ceon had a rare disease called severe combined immunodeficiency (SCID), also known as bubble-baby disease.

 

Ja’Ceon Golden is treated by patient care assistant Grace Deng (center) and pediatric oncology nurse Kat Wienskowski. Photo: Santiago Mejia, The Chronicle.

Babies with SCID lack the body’s immune defenses against infectious diseases and are forced to live in a sterile environment. Without early treatment, SCID babies often die within one year due to recurring infections. Bone marrow transplantation is the most common treatment for SCID, but it’s only effective if the patient has a donor that is a perfect genetic match, which is only possible for about one out of five babies with this disease.

Advances in gene therapy are giving SCID babies like Ja’Ceon hope for safer, more effective cures. The SF Chronicle piece highlights two CIRM-funded clinical trials for SCID run by UCLA in collaboration with UCSF and St. Jude Children’s Research Hospital. In these trials, scientists isolate the bone marrow stem cells from SCID babies, correct the genetic mutation causing SCID in their stem cells, and then transplant them back into the patient to give them a healthy new immune system.

The initial results from these clinical trials are promising and support other findings that gene therapy could be an effective treatment for certain genetic diseases. CIRM’s Senior Science Officer, Sohel Talib, was quoted in the Chronicle piece saying,

“Gene therapy has been shown to work, the efficacy has been shown. And it’s safe. The confidence has come. Now we have to follow it up.”

Ja’Ceon was the first baby treated at the UCSF Benioff Children’s Hospital and so far, he is responding well to the treatment. His great aunt Dannie Hawkins said that it was initially hard for her to enroll Ja’Ceon in this trial because she was a partial genetic match and had the option of donating her own bone-marrow to help save his life. In the end, she decided that his involvement in the trial would “open the door for other kids” to receive this treatment if it worked.

Ja’Ceon Golden plays with patient care assistant Grace Deng in a sterile play area at UCSF Benioff Children’s Hospital.Photo: Santiago Mejia, The Chronicle

It’s brave patients and family members like Ja’Ceon and Dannie that make it possible for research to advance from clinical trials into effective treatments for future patients. We at CIRM are eternally grateful for their strength and the sacrifices they make to participate in these trials.

A Clinical Trial Network Focused on Stem Cell Treatments is Expanding

Geoff Lomax is a Senior Officer of CIRM’s Strategic Initiatives.

California is one of the world-leaders in advancing stem cell research towards treatments and cures for patients with unmet medical needs. California has scientists at top universities and companies conducting cutting edge research in regenerative medicine. It also has CIRM, California’s Stem Cell Agency, which funds promising stem cell research and is advancing stem cell therapies into clinical trials. But the real clincher is that California has something that no one else has: a network of medical centers dedicated to stem cell-based clinical trials for patients. This first-of-its-kind system is called the CIRM Alpha Stem Cell Clinics Network.

Get to Know Our Alpha Clinics

In 2014, CIRM launched its Alpha Stem Cell Clinics Network to accelerate the development and delivery of stem cell treatments to patients. The network consists of three Alpha Clinic sites at UC San Diego, City of Hope in Duarte, and a joint clinic between UC Los Angeles and UC Irvine. Less than three years since its inception, the Alpha Clinics are conducting 34 stem cell clinical trials for a diverse range of diseases such as cancer, heart disease and sickle cell anemia. You can find a complete list of these clinical trials on our Alpha Clinics website. Below is an informational video about our Alpha Clinics Network.

So far, hundreds of patients have been treated at our Alpha Clinics. These top-notch medical centers use CIRM-funding to build teams specialized in overseeing stem cell trials. These teams include patient navigators who provided in-depth information about clinical trials to prospective patients and support them during their treatment. They also include pharmacists who work with patients’ cells or manufactured stem cell-products before the therapies are given to patients. And lastly, let’s not forget the doctors and nurses that are specially trained in the delivery of stem cell therapies to patients.

The Alpha Clinics Network also offers resources and tools for clinical trial sponsors, the people responsible for conducting the trials. These include patient education and recruitment tools and access to over 20 million patients in California to support successful recruitment. And because the different clinical trial sites are in the same network, sponsors can benefit from sharing the same approval measures for a single trial at multiple sites.

Looking at the big picture, our Alpha Clinics Network provides a platform where patients can access the latest stem cell treatments, and sponsors can access expert teams at multiple medical centers to increase the likelihood that their trial succeeds.

The Alpha Clinics Network is expanding

This collective expertise has resulted in a 3-fold (from 12 to 36 – two trials are being conducted at two sites) increase in the number of stem cell clinical trials at the Alpha Clinic sites since the Network’s inception. And the number continues to rise every quarter. Given this impressive track record, CIRM’s Board voted in February to expand our Alpha Clinics Network. The Board approved up to $16 million to be awarded to two additional medical centers ($8 million each) to create new Alpha Clinic sites and work with the current Network to accelerate patient access to stem cell treatments.

CIRM’s Chairman Jonathan Thomas explained,

Jonathan Thomas

“We laid down the foundation for conducting high quality stem cell trials when we started this network in 2014. The success of these clinics in less than three years has prompted the CIRM Board to expand the Network to include two new trial sites. With this expansion, CIRM is building on the current network’s momentum to establish new and better ways of treating patients with stem cell-based therapies.”

The Alpha Clinics Network plays a vital role in CIRM’s five-year strategic plan to fund 50 new clinical trials by 2020. In fact, the Alpha Clinic Network supports clinical trials funded by CIRM, industry sponsors and other sources. Thus, the Network is on track to becoming a sustainable resource to deliver stem cell treatments indefinitely.

In addition to expanding CIRM’s Network, the new sites will develop specialized programs to train doctors in the design and conduct of stem cell clinical trials. This training will help drive the development of new stem cell therapies at California medical centers.

Apply to be one our new Alpha Clinics!

For the medical centers interested in joining the CIRM Alpha Stem Cell Clinics Network, the deadline for applications is May 15th, 2017. Details on this funding opportunity can be found on our funding page.

The CIRM Team looks forward to working with prospective applicants to address any questions. The Alpha Stem Cell Clinics Network will also be showcasing it achievement at its Second Annual Symposium, details may be found on the City of Hope Alpha Clinics website.

City of Hope Medical Center and Alpha Stem Cell Clinic


Related Links:

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.

Raising awareness about Rare Disease Day

rare-disease-day-logo

One of the goals we set ourselves at CIRM in our 2016 Strategic Plan was to fund 50 new clinical trials over the next five years, including ten rare or orphan diseases. Since then we have funded 13 new clinical trials including four targeting rare diseases (retinitis pigmentosa, severe combined immunodeficiency, ALS or Lou Gehrig’s disease, and Duchenne’s Muscular Dystrophy). It’s a good start but clearly, with almost 7,000 rare diseases, this is just the tip of the iceberg. There is still so much work to do.

And all around the world people are doing that work. Today we have asked Emily Walsh, the Community Outreach Director at the Mesothelioma Cancer Alliance,  to write about the efforts underway to raise awareness about rare diseases, and to raise funds for research to develop new treatments for them.

“February 28th marks the annual worldwide event for Rare Disease Day. This is a day dedicated to raising awareness for rare diseases that affect people all over the world. The campaign works to target the general public as well as policy makers in hopes of bringing attention to diseases that receive little attention and funding. For the year 2017 it was decided that the focus would fall on “research,” with the slogan, “With research, possibilities are limitless.”

Getting involved for Rare Disease Day means taking this message and spreading it far and wide. Awareness for rare diseases is extremely important, especially among researchers, universities, students, companies, policy makers, and clinicians. It has long been known that the best advocates for rare diseases are the patients themselves. They use their specific perspectives to raise their voice, share their story, and shed light on the areas where additional funding and research are most necessary.

To see how you can help support the Rare Disease Day efforts this year, click here.

Groups like the Mesothelioma Cancer Alliance and the Mesothelioma Group are adding their voices to the cause to raise awareness about mesothelioma cancer, a rare form of cancer caused by exposure and inhalation of airborne asbestos fibers

Rare diseases affect 300 million people worldwide, but only 5% of them have an FDA approved treatment or cure. Malignant mesothelioma is among the 95 percent that doesn’t have a treatment or cure.

Asbestos has been used throughout history in building materials because of its fire retardant properties. Having a home with asbestos insulation, ceiling tiles, and roof shingles meant that the house was safer. However, it was found that once asbestos crumbled and became powder-like, the tiny fibers could become airborne and be inhaled and lodge themselves in lung tissue causing mesothelioma. The late stage discovery of mesothelioma is often what causes it to have such a high mortality rate. Symptoms can have a very sudden onset, even though the person may have been exposed decades prior.

Right now, treatment for mesothelioma includes the usual combination of chemotherapy, radiation, and surgery, but researchers are looking at other approaches to see if they can be more effective or can help in conjunction with the standard methods. For example one drug, Defactinib, has shown some promise in inhibiting the growth and spread of cancer stem cells – these are stem cells that can evade chemotherapy and cause patients to relapse.”

Some people might ask why spend limited resources on something that affects so few people. But the lessons we learn in developing treatments for a rare disease can often lead us to treatments for diseases that affect many millions of people.

But numbers aside, there is no hierarchy of need, no scale to say the suffering of people with Huntington’s disease is any greater or less than that of people with Alzheimer’s. We are not in the business of making value judgements about who has the greatest need. We are in the business of accelerating treatments to patients with unmet medical needs. And those suffering from rare disease are very clearly  people in need.

 


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Stem cells stories that caught our eye: switching cell ID to treat diabetes, AI predicts cell fate, stem cell ALS therapy for Canada

Treating diabetes by changing a cell’s identity. Stem cells are an ideal therapy strategy for treating type 1 diabetes. That’s because the disease is caused by the loss of a very specific cell type: the insulin-producing beta cell in the pancreas. So, several groups are developing treatments that aim to replace the lost cells by transplanting stem cell-derived beta cells grown in the lab. In fact, Viacyte is applying this approach in an ongoing CIRM-funded clinical trial.

In preliminary animal studies published late last week, a Stanford research team has shown another approach may be possible which generates beta cells inside the body instead of relying on cells grown in a petri dish. The CIRM-funded Cell Metabolism report focused on alpha cells, another cell type in pancreas which produces the hormone glucagon.

glucagon

Microscopy of islet cells, round clusters of cells found in the pancreas. The brown stained cells are glucagon-producing alpha cells. Credit: Wikimedia Commons

After eating a meal, insulin is critical for getting blood sugar into your cells for their energy needs. But glucagon is needed to release stored up sugar, or glucose, into your blood when you haven’t eaten for a while. The research team, blocked two genes in mice that are critical for maintaining an alpha cell state. Seven weeks after inhibiting the activity of these genes, the researchers saw that many alpha cells had converted to beta cells, a process called direct reprogramming.

Does the same thing happen in humans? A study of cadaver donors who had been recently diagnosed with diabetes before their death suggests the answer is yes. An analysis of pancreatic tissue samples showed cells that produced both insulin and glucagon, and appeared to be in the process of converting from beta to alpha cells. Further genetic tests showed that diabetes donor cells had lost activity in the two genes that were blocked in the mouse studies.

It turns out that there’s naturally an excess of alpha cells so, as team lead Seung Kim mentioned in a press release, this strategy could pan out:

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Seung Kim. Credit: Steve Fisch, Stanford University

“This indicates that it might be possible to use targeted methods to block these genes or the signals controlling them in the pancreatic islets of people with diabetes to enhance the proportion of alpha cells that convert into beta cells.”

Using computers to predict cell fate. Deep learning is a cutting-edge area of computer science that uses computer algorithms to perform tasks that border on artificial intelligence. From beating humans in a game of Go to self-driving car technology, deep learning has an exciting range of applications. Now, scientists at Helmholtz Zentrum München in Germany have used deep learning to predict the fate of cells.

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Using deep learning, computers can predict the fate of these blood stem cells.
Credit: Helmholtz Zentrum München.

The study, published this week in Nature Methods, focused on blood stem cells also called hematopoietic stem cells. These cells live in the bone marrow and give rise to all the different types of blood cells. This process can go awry and lead to deadly disorders like leukemia, so scientists are very interested in exquisitely understanding each step that a blood stem cell takes as it specializes into different cell types.

Researchers can figure out the fate of a blood stem cells by adding tags, which glow with various color, to the cell surface . Under a microscope these colors reveal the cells identity. But this method is always after the fact. There no way to look at a cell and predict what type of cell it is turning into. In this study, the team filmed the cells under a microscope as they transformed into different cell types. The deep learning algorithm processed the patterns in the cells and developed cell fate predictions. Now, compared to the typical method using the glowing tags, the researchers knew the eventual cell fates much sooner. The team lead, Carsten Marr, explained how this new technology could help their research:

“Since we now know which cells will develop in which way, we can isolate them earlier than before and examine how they differ at a molecular level. We want to use this information to understand how the choices are made for particular developmental traits.”

Stem cell therapy for ALS seeking approval in Canada. (Karen Ring) Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease that kills off the nerve cells responsible for controlling muscle movement. Patients with ALS suffer from muscle weakness, difficulty in speaking, and eventually breathing. There is no cure for ALS and the average life expectancy after diagnosis is just 2 – 5 years. But companies are pursuing stem cell-based therapies in clinical trials as promising treatment options.

One company in particular, BrainStorm Cell Therapeutics based in the US and Israel, is testing a mesenchymal stem cell-based therapy called NurOwn in ALS patients in clinical trials. In their Phase 2 trials, they observed clinical improvements in slowing down the rate of disease progression following the stem cell treatment.

In a recent update from our friends at the Signals Blog, BrainStorm has announced that it is seeking regulatory approval of its NurOwn treatment for ALS patients in Canada. They will be working with the Centre for Commercialization of Regenerative Medicine (CCRM) to apply for a special regulatory approval pathway with Health Canada, the Canadian government department responsible for national public health.

In a press release, BrainStorm CEO Chaim Lebovits, highlighted this new partnership and his company’s mission to gain regulatory approval for their ALS treatment:

“We are pleased to partner with CCRM as we continue our efforts to develop and make NurOwn available commercially to patients with ALS as quickly as possible. We look forward to discussing with Health Canada staff the results of our ALS clinical program to date, which we believe shows compelling evidence of safety and efficacy and may qualify for rapid review under Canada’s regulatory guidelines for drugs to treat serious or life-threatening conditions.”

Stacey Johnson who wrote the Signals Blog piece on this story explained that while BrainStorm is not starting a clinical trial for ALS in Canada, there will be significant benefits if its treatment is approved.

“If BrainStorm qualifies for this pathway and its market authorization request is successful, it is possible that NurOwn could be available for patients in Canada by early 2018.  True access to improved treatments for Canadian ALS patients would be a great outcome and something we are all hoping for.”

CIRM is also funding stem cell-based therapies in clinical trials for ALS. Just yesterday our Board awarded Cedars-Sinai $6.15 million dollars to conduct a Phase 1 trial for ALS patients that will use “cells called astrocytes that have been specially re-engineered to secrete proteins that can help repair and replace the cells damaged by the disease.” You can read more about this new trial in our latest news release.

Partnering with the best to help find cures for rare diseases

As a state agency we focus most of our efforts and nearly all our money on California. That’s what we were set up to do. But that doesn’t mean we don’t also look outside the borders of California to try and find the best research, and the most promising therapies, to help people in need.

Today’s meeting of the CIRM Board was the first time we have had a chance to partner with one of the leading research facilities in the country focusing on children and rare diseases; St. Jude Children’s Researech Hospital in Memphis, Tennessee.

a4da990e3de7a2112ee875fc784deeafSt. Jude is getting $11.9 million to run a Phase I/II clinical trial for x-linked severe combined immunodeficiency disorder (SCID), a catastrophic condition where children are born without a functioning immune system. Because they are unable to fight off infections, many children born with SCID die in the first few years of life.

St. Jude is teaming up with researchers at the University of California, San Francisco (UCSF) to genetically modify the patient’s own blood stem cells, hopefully creating a new blood system and repairing the damaged immune system. St. Jude came up with the method of doing this, UCSF will treat the patients. Having that California component to the clinical trial is what makes it possible for us to fund this work.

This is the first time CIRM has funded work with St. Jude and reflects our commitment to moving the most promising research into clinical trials in people, regardless of whether that work originates inside or outside California.

The Board also voted to fund researchers at Cedars-Sinai to run a clinical trial on ALS or Lou Gehrig’s disease. Like SCID, ALS is a rare disease. As Randy Mills, our President and CEO, said in a news release:

CIRM CEO and President, Randy Mills.

CIRM CEO and President, Randy Mills.

“While making a funding decision at CIRM we don’t just look at how many people are affected by a disease, we also look at the severity of the disease on the individual and the potential for impacting other diseases. While the number of patients afflicted by these two diseases may be small, their need is great. Additionally, the potential to use these approaches in treating other disease is very real. The underlying technology used in treating SCID, for example, has potential application in other areas such as sickle cell disease and HIV/AIDS.”

We have written several blogs about the research that cured children with SCID.

The Board also approved funding for a clinical trial to develop a treatment for type 1 diabetes (T1D). This is an autoimmune disease that affects around 1.25 million Americans, and millions more around the globe.

T1D is where the body’s own immune system attacks the cells that produce insulin, which is needed to control blood sugar levels. If left untreated it can result in serious, even life-threatening, complications such as vision loss, kidney damage and heart attacks.

Researchers at Caladrius Biosciences will take cells, called regulatory T cells (Tregs), from the patient’s own immune system, expand the number of those cells in the lab and enhance them to make them more effective at preventing the autoimmune attack on the insulin-producing cells.

The focus is on newly-diagnosed adolescents because studies show that at the time of diagnosis T1D patients usually have around 20 percent of their insulin-producing cells still intact. It’s hoped by intervening early the therapy can protect those cells and reduce the need for patients to rely on insulin injections.

David J. Mazzo, Ph.D., CEO of Caladrius Biosciences, says this is hopeful news for people with type 1 diabetes:

David Mazzo

David Mazzo

“We firmly believe that this therapy has the potential to improve the lives of people with T1D and this grant helps us advance our Phase 2 clinical study with the goal of determining the potential for CLBS03 to be an effective therapy in this important indication.”

 


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