The Stem Cell Bank is open for business

Creating a stem cell bank

Creating a stem cell bank

When you go to a bank and withdraw money you know that the notes you get are all going to look the same and do the same job, namely allow you to buy things. But when you get stem cells for research that’s not necessarily the case. Stem cells bought from different laboratories don’t always look exactly the same or perform the same in research studies.

That’s why CIRM has teamed up with the Coriell Institute and Cellular Dynamics International (CDI) to open what will be the world’s largest publically available stem cell bank. It officially opened today. In September the Bank will have 300 cell lines available for purchase but plans to increase that to 750 by February 2016.

300 lines but no waiting

Now, even if you are not in the market for stem cells this bank could have a big impact on your life because it creates an invaluable resource for researchers looking into the causes of, and potential therapies for, 11 different diseases including autism, epilepsy and other childhood neurological disorders, blinding eye diseases, heart, lung and liver diseases, and Alzheimer’s disease.

The goal of the Bank – which is located at the Buck Institute for Research on Aging in Novato, California – is to collect blood or tissue samples from up to 3,000 volunteer donors. Some of those donors have particular disorders – such as Alzheimer’s – and some are healthy. Those samples will then be turned into high quality iPSCs or induced pluripotent stem cells.

Now, iPSC lines are particularly useful for research because they can be turned into any type of cell in the body such as a brain cell or liver cell. And, because the cells are genetically identical to the people who donated the samples scientists can use the cells to determine how, for example, a brain cell from someone with autism differs from a normal brain cell. That can enable them to study how diseases develop and progress, and also to test new drugs or treatments against defects observed in those cells to see which, if any, might offer some benefits.

Power of iPSCs

In a news release Kaz Hirao, Chairman and CEO of CDI, says these could be game changers:

“iPSCs are proving to be powerful tools for disease modeling, drug discovery and the development of cell therapies, capturing human disease and individual genetic variability in ways that are not possible with other cellular models.”

Equally important is that researchers in different parts of the world will be able to compare their findings because they are using the same cell lines. Right now many researchers use cell lines from different sources so even though they are theoretically the same type of tissue, in practice they often produce very different results.

Improving consistency

CIRM Board Chair, Jonathan Thomas, said he hopes the Bank will lead to greater consistency in results.

“We believe the Bank will be an extraordinarily important resource in helping advance the use of stem cell tools for the study of diseases and finding new ways to treat them. While many stem cell efforts in the past have provided badly needed new tools for studying rare genetic diseases, this Bank represents both rare and common diseases that afflict many Californians. Stem cell technology offers a critical new approach toward developing new treatments and cures for those diseases as well.”

Most banks are focused on enriching your monetary account. This bank hopes to enrich people’s lives, by providing the research tools needed to unlock the secrets of different diseases, and pave the way for new treatments.

For more information on how to buy a cell line go to http://catalog.coriell.org/CIRM or email CIRM@Coriell.org

Cell mate: the man who makes stem cells for clinical trials

When we announced that one of the researchers we fund – Dr. Henry Klassen at the University of California, Irvine – has begun his clinical trial to treat the vision-destroying disease retinitis pigmentosa, we celebrated the excitement felt by the researchers and the hope from people with the disease.

But we missed out one group. The people who make the cells that are being used in the treatment. That’s like praising a champion racecar driver for their skill and expertise, and forgetting to mention the people who built the car they drive.

Prof. Gerhard Bauer

Prof. Gerhard Bauer

In this case the “car” was built by the Good Manufacturing Practice (GMP) team, led by Prof. Gerhard Bauer, at the University of California Davis (UC Davis).

Turns out that Gerhard and his team have been involved in more than just one clinical trial and that the work they do is helping shape stem cell research around the U.S. So we decided to get the story behind this work straight from the horse’s mouth (and if you want to know why that’s a particularly appropriate phrase to use here read this previous blog about the origins of GMP)

When did the GMP facility start, what made you decide this was needed at UC Davis?

Gerhard: In 2006 the leadership of the UC Davis School of Medicine decided that it would be important for UC Davis to have a large enough manufacturing facility for cellular and gene therapy products, as this would be the only larger academic GMP facility in Northern CA, creating an important resource for academia and also industry. So, we started planning the UC Davis Institute for Regenerative Cures and large GMP facility with a team of facility planners, architects and scientists, and by 2007 we had our designs ready and applied for the CIRM major facilities grant, one of the first big grants CIRM offered. We were awarded the grant and started construction in 2008. We opened the Institute and GMP facility in April of 2010.

How does it work? Do you have a number of different cell lines you can manufacture or do people come to you with cell lines they want in large numbers?

Gerhard: We perform client driven manufacturing, which means the clients tell us what they need manufactured. We will, in conjunction with the client, obtain the starting product, for instance cells that need to undergo a manufacturing process to become the final product. These cells can be primary cells or also cell lines. Cell lines may perhaps be available commercially, but often it is necessary to derive the primary cell product here in the GMP facility; this can, for instance, be done from whole donor bone marrow, from apheresis peripheral blood cells, from skin cells, etc.

How many cells would a typical – if there is such a thing – order request?

Gerhard: This depends on the application and can range from 1 million cells to several billions of cells. For instance, for an eye clinical trial using autologous (from the patient themselves) hematopoietic stem and progenitor cells, a small number, such as a million cells may be sufficient. For allogeneic (from an unrelated donor) cell banks that are required to treat many patients in a clinical trial, several billion cells would be needed. We therefore need to be able to immediately and adequately adjust to the required manufacturing scale.

Why can’t researchers just make their own cells in their own lab or company?

Gerhard: For clinical trial products, there are different, higher, standards than apply for just research laboratory products. There are federal regulations that guide the manufacturing of products used in clinical trials, in this special case, cellular products. In order to produce such products, Good Manufacturing Practice (GMP) rules and regulations, and guidelines laid down by both the Food and Drug Administration (FDA) and the United States Pharmacopeia need to be followed.

The goal is to manufacture a safe, potent and non-contaminated product that can be safely used in people. If researchers would like to use the cells or cell lines they developed in a clinical trial they have to go to a GMP manufacturer so these products can actually be used clinically. If, however, they have their own GMP facility they can make those products in house, provided of course they adhere to the rules and regulations for product manufacturing under GMP conditions.

Besides the UC Irvine retinitis pigmentosa trial now underway what other kinds of clinical trials have you supplied cells for?

Gerhard: A UC Davis sponsored clinical trial in collaboration with our Eye Center for the treatment of blindness (NCT01736059), which showed remarkable vision recovery in two out of the six patients who have been treated to date (Park et al., PMID:25491299, ), and also an industry sponsored clinical gene therapy trial for severe kidney disease. Besides cellular therapy products, we also manufacture clinical grade gene therapy vectors and specialty drug formulations.

For several years we have been supplying clinicians with a UC Davis GMP facility developed formulation of the neuroactive steroid “allopregnanolone” that was shown to act on resident neuronal stem cells. We saved several lives of patients with intractable seizures, and the formulation is also applied in clinical trials for the treatment of traumatic brain injury, Fragile X syndrome and Alzheimer’s disease.

What kinds of differences are you seeing in the industry, in the kinds of requests you get now compared to when you started?

Gerhard: In addition, gene therapy vector manufacturing and formulation work is really needed by several clients. One of the UC Davis specialties is “next generation” gene-modified mesenchymal stem cells, and we are contacted often to develop those products.

Where will we be in five years?

Gerhard: Most likely, some of the Phase I/II clinical trials (these are early stage clinical trials with, usually, relatively small numbers of patients involved) will have produced encouraging results, and product manufacturing will need to be scaled up to provide enough cellular products for Phase III clinical trials (much larger trials with many more people) and later for a product that can be licensed and marketed.

We are already working with companies that anticipate such scale up work and transitioning into manufacturing for marketing; we are planning this upcoming process with them. We also believe that certain cellular products will replace currently available standard medical treatments as they may turn out to produce superior results.

What does the public not know about the work you do that you think they should know?

Gerhard: The public should know that UC Davis has the largest academic Good Manufacturing Practice Facility in Northern California, that its design was well received by the FDA, that we are manufacturing a wide variety of products – currently about 16 – that we are capable of manufacturing several products at one time without interfering with each other, and that we are happy to work with clients from both academia and private industry through both collaborative and Fee-for-Service arrangements.

We are also very proud to have, during the last 5 years, contributed to saving several lives with some of the novel products we manufactured. And, of course, we are extremely grateful to CIRM for building this state-of-the-art facility.

You can see a video about the building of the GMP facility at UC Davis here.

Researchers cool to idea of ice bath after exercise

Have you ever had a great workout, really pushed your body and muscles hard and thought “You know what would be good right now? A nice plunge into an ice bath.”

No. Me neither.

Weightlifter Karyn Marshall taking an ice bath: Photo courtesy Karyn Marshall

Weightlifter Karyn Marshall taking an ice bath: Photo courtesy Karyn Marshall

But some people apparently believe that taking an ice bath after a hard workout can help their muscles rebound and get stronger.

It’s a mistaken belief, at least according to a new study from researchers at the Queensland University of Technology (QUT) and the University of Queensland (UQ) in Australia. They are – pardon the pun – giving the cold shoulder to the idea that an ice bath can help hot muscles recover after a hard session of strength training.

The researchers got 21 men who exercise a lot to do strength training twice a week for 12 weeks. One group then agreed – and I’d love to know how they persuaded them to do this – to end the training session by jumping into a 50 degrees Fahrenheit (10 Celsius) ice bath. The other group – let’s label them the “sensible brigade” – ended by doing their cool down on an exercise bike.

Happily for the rest of us at the end of the 12 weeks the “sensible brigade” experienced more gains in muscle strength and muscle mass than the cool kids.

So what does this have to do with stem cells? Well the researchers say the reason for this result is because our bodies use so-called satellite cells – which are a kind of muscle stem cell – to help build stronger muscles. When you plunge those muscles into a cold bath you effectively blunt or block the ability of the muscle stem cells to work as well as they normally would.

But the researchers weren’t satisfied just putting that particular theory on ice, so in a second study they took muscle biopsies from men after they had done leg-strengthening exercises. Again, half did an active cool down, the others jumped in the ice bath.

In a news release accompanying the article in the The Journal of Physiology, Dr Llion Roberts, from UQ’s School of Human Movement and Nutrition Sciences, said the results were the same:

“We found that cold water immersion after training substantially attenuated, or reduced, long-term gains in muscle mass and strength. It is anticipated that athletes who use ice baths after workouts would see less long-term muscle gains than those who choose an active warm down.”

The bottom line; if you strain a muscle working out ice is your friend because it’s great for reducing inflammation. If you want to build stronger muscles ice is not your friend. Save it for that nice refreshing beverage you have earned after the workout.

Cheers!

Da Mayor and the clinical trial that could help save his vision

Former San Francisco Mayor and California State Assembly Speaker Willie Brown is many things, but shy is not one of them. A profile of him in the San Francisco Chronicle once described him as “Brash, smart, confident”. But for years Da Mayor – as he is fondly known in The City – said very little about a condition that is slowly destroying his vision. Mayor Brown has retinitis pigmentosa (RP).

RP is a degenerative disease that slowly destroys a person’s sight vision by attacking and destroying photoreceptors in the retina, the light-sensitive area at the back of the eye that is critical for vision. At a recent conference held by the Everylife Foundation for Rare Diseases, Mayor Brown gave the keynote speech and talked about his life with RP.

Willie Brown

He described how people thought he was being rude because he would walk by them on the streets and not say hello. The truth is, he couldn’t see them.

He was famous for driving fancy cars like Bentleys, Maseratis and Ferraris. When he stopped doing that, he said, “people thought I was broke because I no longer had expensive cars.” The truth is his vision was too poor for him to drive.

Despite its impact on his life RP hasn’t slowed Da Mayor down, but now there’s a new clinical trial underway that might help him, and others like him, regain some of that lost vision.

The trial is the work of Dr. Henry Klassen at the University of California, Irvine (UCI). Dr. Klassen just announced the treatment of their first four patients, giving them stem cells that hopefully will slow down or even reverse the progression of RP.

“We are delighted to be moving into the clinic after many years of bench research,” Klassen said in a news release.

The patients were each given a single injection of retinal progenitor cells. It’s hoped these cells will help protect the photoreceptors in the retina that have not yet been damaged by RP, and even revive those that have become impaired but not yet destroyed by the disease.

The trial will enroll 16 patients in this Phase 1 trial. They will all get a single injection of retinal cells into the eye most affected by the disease. After that, they’ll be followed for 12 months to make sure that the therapy is safe and to see if it has any beneficial effects on vision in the treated eye, compared to the untreated one.

In a news release Jonathan Thomas, Ph.D., J.D., Chair of the CIRM Board said it’s always exciting when a therapy moves out of the lab and into people:

“This is an important step for Dr. Klassen and his team, and hopefully an even more important one for people battling this devastating disease. Our mission at CIRM is to accelerate the development of stem cell therapies for patients with unmet medical needs, and this certainly fits that bill. That’s why we have invested almost $19 million in helping this therapy reach this point.”

RP hasn’t defeated Da Mayor. Willie Brown is still known as a sharp dresser and an even sharper political mind. His message to the people at the Everylife Foundation conference was, “never give up, keep striving, keep pushing, keep hoping.”

To learn more about the study or to enroll contact the UCI Alpha Stem Cell Clinic at 949-824-3990 or by email at stemcell@uci.edu.

And visit our website to watch a presentation about the trial (link) by Dr. Klassen and to hear brief remarks from one of his patients.

Creativity sparks a bright future for science

When some people want to see the future they use a crystal ball. Others use tarot cards or runes. But when anyone at CIRM wants to see the future all we have to do is look into the faces of the students in our Creativity program.

Creativity students 2015 with program director Dr. Mani Vessal (front & center with tie)

Creativity students 2015 with program director Dr. Mani Vessal (front & center with tie)

Over the past three years the Creativity program has given some 220 California high school students a chance to spend the summer working in a world-class stem cell research facility. And when I say work, I mean work. They are required to attend lectures, grow their own stem cells, and do experiments. In short, they are expected to do what all the other scientists in the lab do. In return they get a great experience, and a modest stipend for their effort. At the end they produce papers on their work with titles like:

  • Notch Signaling as a Possible Regulator of Mesenchymal Stromal Cell Differentiation in the Hematopoietic Stem Cell Niche
  • RNA Splicing Factor ZRSR2 in Human Erythroleukemia and Stem Cells

We also ask the students to either write a blog or create a video about their experiences over the summer. Many do both. We’ll come back to the video portion later this week. The blogs make for a great read because they chart the students as they progress from knowing little if anything about stem cells, to being quite proficient at working with them. And all in just 8 weeks. One of the hardest parts of our job is choosing the best blog. For example Alice Lin, part of the City of Hope program, got an honorable mention for her blog that was a “diary” written by an embryonic stem cell. Here’s a small sample of her approach:

‘Also, this is NOT YOUR TYPICAL LAB JOURNAL ENTRY. It’s an autobiography chronicling my life. That way, when the stem cell controversy cools down, the general public can get a FIRST HAND ACCOUNT of what we do. This blog is going to rack up some serious views someday. Until then, I’m attached to my colony and the plate.’

Ryan Hale, part of the Scripps team, wrote about how the experience taught him to think like a scientist:

‘One day, after performing an experiment, our mentor asked us the reason behind our experiment. He wasn’t asking us about the experimental procedure or quizzing us on the pre-reading packet, he wanted us to understand the thought process a researcher would go through to actually think up such an experiment… Our mentor stressed how important it is to be creative, inquisitive, and critical if one wants to become a successful researcher.’

Selena Zhang

Selena Zhang

The winner was Selena Zhang, also part of the City of Hope team. She writes about her experiences in the lab, learning the ropes, getting to understand the technology and language of science. But it’s her closing paragraph that sealed the deal for us. In a few short sentences she manages to capture the romance, the mystery and the magic of science. And we’re also happy to say that this program is coming back next year, and the year after that, for five more years. Our Board has just approved renewed funding. The name of the program is changing, it will be called SPARK, but the essence will remain the same. Giving young students a glimpse at a future in science. You don’t need a crystal ball to know that with these students the future is bright. Here’s Selena’s winning blog:

My very own lab coat. It was a lot to live up to, my freshly laundered lab coat with the City of Hope logo. Looking around the lab, I was nervous and excited to start my very first day. There were papers to read and meetings with my mentor to hear about my project. I was starstruck, as I learned that I would be working with induced pluripotent stem cells, Alzheimer’s disease, and CRISPR. Terms that seemed to only exist in textbooks and science magazines that I lovingly read at the library were suddenly alive to me. Although, embarrassingly enough, the only thing that came to mind when my mentor mentioned CRISPR was a salad crisper. Fairly certain that she was a) speaking about something else and b) that I needed to eat more for breakfast, I asked her what that was. It turned out that CRISPR was a new genome editing tool we could use to create isogenic lines to study the independent effects of each allele of the APOE gene that is the most significant risk factor for Alzheimer’s. We would do this by converting a patient and wild-type fibroblast into induced pluripotent stem cells. From this, we would edit a normal allele into the patient’s cell for rescue and the mutated allele in the wild-type cell for insertion, respectively. We would eventually differentiate these cells into neurons and astrocytes to study how the change of this allele can impact neural interaction. This was real science in progress, not enshrined in a textbook, but free, fluid, and vibrant. I slowly grew into my own independence around the lab. I found myself more confident and emotionally invested with each experiment, every immunostaining and PCR. Science, for all of its realism, had always seemed like the unimaginable fantasy to me. Through this opportunity, science has become more tangible, grounded in unglamorous details: hard work and deadlines, mistakes and mishaps, long lab meetings and missed lunches. Yet, that has only made me more confident that I want to pursue science. Now, I’m embracing a reality, one that gives me something worth striving for. In fact, I am very fortunate that my project has encountered numerous obstacles. My initial response to these problems was and still is a lot less Zen and a lot more panic-driven. But I’ve slowly come to realize the beauty of the troubleshooting process for progress. My project has been an emotional rollercoaster, as our rescue cell line met success, but couldn’t advance to the next stage. Our insertion cell line appeared to have incorporated the mutation, but it turned out it only incorporated one allele. It’s been a process of finding the balance between defending our ideas and accepting new ones, the border between defending and defensiveness. My curiosity and drive to improve, to understand, to conquer the unknown is learning to coexist with the need for patience and flexibility No matter how solid our theory should have been, reality is fickle and all the more interesting for it. I thought science was all about doubt and skepticism, questioning everything. Through this internship, I’ve learned that there’s also a surprising amount of faith, the faith to accept any setbacks as part of the discovery process. I thought I loved science before because I loved how enough facts could help me make sense of things. But through this internship in the lab, I’m learning to love a larger part of science, which is not only loving knowledge, but also loving not knowing, loving discovery for all of its uncertainty and perfect imperfections. I’m learning to grow into my lab coat, and hopefully, to find my place in the field of science.

Bridging the gap: training scientists to speak everyday English

Getting a start in your chosen career is never easy. Without experience it’s hard to get a job. And without a job you can’t get experience. That’s why the CIRM Bridges program was created, to help give undergraduate and Master’s level students a chance to get the experience they need to start a career in stem cell research.

Last week our governing Board approved a new round of funding for this program, ensuring it will continue for another 5 years.

But we are not looking to train just any student; we are looking to recruit and retain students who reflect the diversity of California, students who might not otherwise have a chance to work in a world-class stem cell research facility.

Want to know what that kind of student looks like? What kind of work they do? Well, the Bridges program at City College of San Francisco recently got its latest group of Bridges students to record an “elevator pitch”; that’s a short video where they explain what they do and why it’s important, in language anyone can understand.

They do a great job of talking about their research in a way that’s engaging and informative; no easy matter when you are discussing things as complex as using stem cells to test whether everyday chemicals can have a toxic impact on the developing brain, or finding ways to turn off the chromosome that causes Down’s syndrome.

Regular readers of the CIRM blog know we are huge supporters of anything that encourages scientists to be better communicators. We feel that anyone who gets public funding for their work has an obligation to be able to explain that work in words the public can understand. This is not just about being responsive, there’s also a certain amount of self-interest here. The better the public understands the work that scientists do, and how that might impact their health, the more they’ll support that work.

That’s why one of the new elements we have added to the Bridges program is a requirement for the students to engage in community outreach and education. We want them to be actively involved in educating diverse communities around California about the importance of stem cell research and the potential benefits for everyone.

We have also added a requirement for the students to be directly engaged with patients. Too often in the past students studied solely in the lab, learning the skills they’ll need for a career in science. But we want them to also understand whom these skills will ultimately benefit; people battling deadly diseases and disorders. The best way to do that is for the students to meet these people face-to-face, at a bone marrow drive or at a health fair for example.

When you have seen the face of someone in need, when you know their story, you are more motivated to find a way to help them. The research, even if it is at a basic level, is no longer about an abstract idea, it’s about someone you know, someone you have met.

Even the early worm gets old: study unlocks a key to aging

A new study poses the question, ‘When does aging really begin?’ One glance in the mirror every morning is enough for me to know that regardless of where it begins I know where it’s going. And it’s not pretty.

But enough about me. Getting back to the question about aging, two researchers at Northwestern University have uncovered some clues that may give us a deeper understanding of aging and longevity, and even lead to new ways of improving quality of life as we get older.

The researchers were focused on C. elegans, a transparent roundworm. They initially thought that aging was a gradual process: that it began slowly and then picked up pace as the animal got older. Instead they found that in C. elegans aging begins just as soon as the animal reaches reproductive maturity. It hits its peak of fertility, and it is all downhill from there.

The researchers say that once C. elegans has finished producing eggs and sperm – ensuring its line will continue – a genetic switch is thrown by germline stem cells. This flipped switch begins the aging process by turning off the ‘heat shock response’; that’s a mechanism the body uses to protect cells from conditions that would normally pose a threat or even be deadly.

In a news release Richard Morimoto, the senior author of the study, says that without that protective mechanism in place the aging process begins:

C. elegans has told us that aging is not a continuum of various events, which a lot of people thought it was. In a system where we can actually do the experiments, we discover a switch that is very precise for aging. All these stress pathways that insure robustness of tissue function are essential for life, so it was unexpected that a genetic switch is literally thrown eight hours into adulthood, leading to the simultaneous repression of the heat shock response and other cell stress responses.”

You read that right. In the case of poor old C. elegans the aging process begins just eight hours into adulthood. Of course the lifespan of the worm is only about 3 weeks so it’s not surprising the aging process kicks in quite so quickly.

To further test their findings the researchers carried out an experiment where they blocked the genetic switch from flipping, and the worm’s protective mechanisms remained strong.

Now, taking findings from something as small as a worm and trying to extrapolate them to larger animals is never easy. Nonetheless understanding what triggers aging in C. elegans could help us figure out if a similar process was taking place at the cellular level in people.

Morimoto says that knowledge might help us develop ways to improve our cellular quality of life and delay the onset of many of the diseases of aging:

“Wouldn’t it be better for society if people could be healthy and productive for a longer period during their lifetime? I am very interested in keeping the quality control systems optimal as long as we can, and now we have a target. Our findings suggest there should be a way to turn this genetic switch back on and protect our aging cells by increasing their ability to resist stress.”

The study is published in the journal Molecular Cell.

Sonic Hedgehog provides pathway to fight blood cancers

Dr. Catriona Jamieson: Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson:
Photo courtesy Moores Cancer Center, UCSD

For a lot of people Sonic Hedgehog is a video game. But for stem cell researcher Dr. Catriona Jamieson it is a signaling pathway in the body that offers a way to tackle and defeat some deadly blood cancers.

Dr. Jamieson – a researcher at the University of California, San Diego (UCSD) – has a paper published online today in The Lancet Haematology that highlights the safety and dosing levels for a new drug to treat a variety of blood cancers. CIRM funding helped Dr. Jamieson develop this work.

The drug targets cancer stem cells, the kind of cell that is believed to be able to lie dormant and evade anti-cancer therapies before springing back into action, causing a recurrence of the cancer. The drug coaxes the cancer stem cells out of their hiding space in the bone marrow and gets them to move into the blood stream where they can be destroyed by chemotherapy.

In a news release Dr. Jamieson says the drug – known by the catchy name of PF-04449913 – uses the sonic Hedgehog signaling pathway, an important regulator of the way we develop, to attack the cancer:

“This drug gets that unwanted house guest to leave and never come back. It’s a significant step forward in treating people with refractory or resistant myeloid leukemia, myelodysplastic syndrome and myelofibrosis. It’s a bonus that the drug can be administered as easily as an aspirin, in a single, daily oral tablet.”

The goal of this first-in-human study was to test the drug for safety; so 47 adults with blood and marrow cancer were given daily doses of the drug for up to 28 days. Those who were able to tolerate the dosage, without experiencing any serious side effects, were then given a higher dose for the next 28 days. Those who experienced problems were taken off the therapy.

Of the 47 people who started the trial in 2010, 28 experienced side effects. However, only three of those were severe. The drug showed signs of clinical activity – meaning it seemed to have an impact on the disease – in 23 people, almost half of those enrolled in the study.

Because of that initial promise it is now being tested in five different Phase 2 clinical trials. Dr. Jamieson says three of those trials are at UCSD:

“Our hope is that this drug will enable more effective treatment to begin earlier and that with earlier intervention, we can alter the course of disease and remove the need for, or improve the chances of success with, bone marrow transplantation. It’s all about reducing the burden of disease by intervening early.”

Improving process drives progress in stem cell research

shutterstock_212888935Process is not a sexy word. No one gets excited thinking about improving a process. Yet behind every great idea, behind every truly effective program is someone who figured out a way to improve the process, to make that idea not just work, but work better.

It’s not glamorous. Sometimes it’s not even pretty. But it is essential.

Yesterday in Oakland our governing Board approved two new concepts to improve our process, to help us fund research in a way that is faster, smarter and ultimately helps us better meet our mission of accelerating the development of stem cell therapies for patients with unmet medical needs.

The new concepts are for Discovery – the earliest stage of research – and the Translational phase, a critical step in moving promising therapies out of the lab and toward clinical trials where they can be tested in people.

In a news release C. Randal Mills, Ph.D., CIRM’s President and CEO, said that these additions built on the work started when the agency launched CIRM 2.0 in January for the clinical phase of research:

“What makes this approach different is that under CIRM 2.0 we are creating a pathway for research, from Discovery to Translational and Clinical, so that if a scientist is successful with their research at one level they are able to move that ahead into the next phase. We are not interested in research just for its own sake. We are interested in research that is going to help us help patients.”

In the Discovery program, for example, we will now be able to offer financial incentives to encourage researchers who successfully complete their work to move it along into the Translational phase – either themselves or by finding a scientific partner willing to take it up and move it forward.

This does a number of things. First it helps create a pipeline for the most promising projects so ideas that in the past might have stopped once the initial study ended now have a chance to move forward. Obviously our hope is that this forward movement will ultimately lead to a clinical trial. That won’t happen with every research program we fund but this approach will certainly increase the possibility that it might.

There’s another advantage too. By scheduling the Discovery and Translational awards more regularly we are creating a grant system that has more predictability, making it easier for researchers to know when they can apply for funding.

We estimate that each year there will be up to 50 Discovery awards worth a total of $53 million; 12 Translation awards worth a total of $40 million; and 12 clinical awards worth around $100 million. That’s a total of more than $190 million every year for research.

This has an important advantage for the stem cell agency too. We have close to $1 billion left in the bank so we want to make sure we spend it as wisely as we can.

As Jonathan Thomas, Ph.D. J.D, the Chair of our Board, said, having this kind of plan helps us better plan our financial future;

“Knowing how often these programs are going to be offered, and how much money is likely to be awarded means the Board has more information to work with in making decisions on where best to allocate our funding.”

The Board also renewed funding for both the Bridges and SPARK (formerly Creativity) programs. These are educational and training programs aimed at developing the next generation of stem cell scientists. The Bridges students are undergraduate or Master’s level students. The SPARK students are all still in high school. Many in both groups come from poor or low-income communities. This program gives them a chance to work in a world-class stem cell research facility and to think about a career in science, something that for many might have been unthinkable without Bridges or SPARK.

Process isn’t pretty. But for the students who can now think about becoming a scientist, for the researchers who can plan new studies, and for the patients who can now envision a potential therapy getting into clinical trials, that process can make all the difference.

Moving Beyond Current CIRM Funding

Delivering on CIRM’s mission of “accelerating stem cell treatments to patients with unmet medical needs” requires the participation of multiple stakeholders to span the research, development, and commercialization phases of bringing a new product to market. In this post, I am pleased to highlight two recent examples of CIRM-funded projects moving beyond their period of CIRM funding by establishing partnerships with industry and investors to further develop the underlying CIRM-funded technology.

In 2000, Dr. Jill Helms, an academic investigator at Stanford University, received a $6.5 million grant from CIRM under an Early Translational award. The title of Dr. Helms’ project was Enhancing Healing via Wnt-Protein Mediated Activation of Endogenous Stem Cells,” and the goal of the award was to develop a novel, protein-based therapeutic platform to accelerate and enhance tissue regeneration through activation of adult stem cells. The five-year award achieved many critical milestones along the way, including the initiation of two preclinical studies aimed at demonstrating the effectiveness of a protein called L-WNT3A to improve the success of spinal fusion surgery and to treat a degradative bone disease called osteonecrosis, both of which represent unmet medical needs.

Helms_bonegraft

Through CIRM funding, Dr. Jill Helms’ team was able to demonstrate that treatment with a protein called L-Wnt3a regenerates and promotes bone formation in animals models (Figs D,F: untreated; Figs E,G: Wnt3a treated). (image credit: Leucht et al. J Bone Joint Surg Am. 2013;95:1278-88)

Dr. Helms’ work attracted considerable interest from the investor community during the lifespan of her grant, and during the final year of her award Dr. Helms’ WNT3A technology platform was successfully spun out of Stanford into a newly created company called Ankasa Regenerative Therapeutics. Ankasa was established with the financial support of Avalon Ventures – a La Jolla based life sciences venture capital firm, Correlation Ventures – an analytics driven venture capital firm, and Heraeus Medical – a diversified global medical device company based in Germany with over $1 billion of annual revenue. Ankasa has raised an initial $8.5 million in the first round of the total $17 million Series A financing to continue the development of the previously CIRM-funded technology.

Moving Radially Branched Deployment_Neurosurgery_Lim

Dr. Daniel Lim’s CIRM-funded BranchPoint Device allows neurosurgeons to deliver cell based therapies to multiple areas of the brain with just one needle penetration.  (image credit: Silvestrini et al. Stereotact Funct Neurosurg 2013;91:92–103)

The second recent example comes from a CIRM Tools & Technology grant to Dr. Daniel Lim, a neurosurgeon at UCSF. Dr. Lim was awarded a $1.8 million grant to develop a more efficient device for transplanting stem cells into the brain, titled Development and Preclinical Testing of New Devices for Cell Transplantation to the Brain.” Dr. Lim successfully developed a platform technology that enables Radially Branched Deployment (RBD) of cells to multiple target locations at variable radial distances and depths along the initial brain penetration tract with real-time interventional magnetic resonance image (iMRI) guidance. This technology is a huge leap forward over the conventional and crude syringe and needle device that are typically used to inject living cells into the brain.

Dr. Lim’s work attracted the attention of Accurexa, a publicly traded medical device company that licensed the CIRM-funded technology from UCSF. Under the guidance of Accurexa, a 510(k) application was submitted to the FDA for the newly coined “BranchPoint Device.” In June of this year, Accurexa successfully raised $2.5 million in equity financing to continue the development and for commercialization of the BranchPoint Device.

Overall, there remains a lack of industry pull for early stage stem cell technologies, however, both Drs. Helms and Lim’s stories represent successful examples of CIRM providing public dollars for early stage research with the resulting potentially life-saving applications attracting interest from investors and companies. These new investors will further fund and develop the technologies well beyond current CIRM funding and, assuming they are successful, deliver them to patients with unmet medical needs.