Creative partnerships that promote progress

Lewis and Clark: great partnerships can change the world

Lewis and Clark: great partnerships can change the world

Having a good partner can turn something good into something truly memorable. Where would Laurel be without Hardy, Lewis without Clark, Butch Cassidy without the Sundance Kid. That’s why the stem cell agency has partnerships on a number of different levels as part of our mission of accelerating the development of stem cell cures to patients with unmet medical needs.

Our latest partnership is with RegMedNet which, in its own words, “provides a unique and unparalleled platform for the regenerative medicine community to share insights, discuss the latest research, and help move the field forward.” With a goal like that why would we not want to support them?

Like us RegMedNet believes that regenerative medicine is going to completely change the way we treat disease, even the way we think about disease. They also believe that progress of the kind we all want is only going to come by bringing together all the key players from the researchers and manufacturers, to the government regulators and, of course, the patient advocates. Each has a vital role to play in moving the field forward and RegMedNet reflects that in both the content it posts online and in the contributors, who represent institutions and companies worldwide.

One of the most important elements in any partnership is understanding, and RegMedNet does a great job of trying to raise awareness about the field, the challenges we all face, and the progress being made. Bringing together so many different perspectives in one spot really helps create a much deeper understanding of regenerative medicine as a whole.

In a few short years regenerative medicine has gone from a relatively small field to a global industry. Our hope is that creating partnerships with like-minded groups around the world, is going to help it get even bigger and, even better.

Countdown to a cure for HIV/AIDS: California leads the way

shutterstock_98186870Not so long ago using the words ‘HIV/AIDS’ and ‘cure’ in the same sentence would have been considered inappropriate, even reckless. Although there were many antiretroviral medications that were effective at helping control the virus, there was nothing that was even remotely close to a cure on the horizon. And those therapies that had been approved were not always readily available, even in the U.S., let alone in the hardest hit countries in Africa.

Today the picture looks quite different. Cure is no longer just a distant dream, it’s a goal. CIRM has two projects that we are funding in clinical trials – one led by Calimmune Inc. and one by City of Hope and Sangamo BioSciences – whose ultimate goal is to replicate the experience of the “Berlin patient” and effectively cure people with the virus.

And we are not alone, the National Institute for Allergy and Infectious Diseases (NIAID) supports a large portfolio of investigator-initiated grants in HIV cure research, including programs to identify where HIV hides, known as the HIV reservoir, and to determine how these hideouts are established and maintained and then to get rid of them.

With this progress in mind we are partnering with the AIDS Project Los Angeles (APLA), Being Alive and the University of Southern California (USC) to host an HIV/AIDS Town Hall event called “Countdown to a Cure: California Leads the Way.”

The goal of the event is to bring together members of the HIV community and leading researchers in the field to talk about the clinical trials that are underway now, and the other approaches that are being tried to cure AIDS.

Speakers at the Town Hall are Dr. Paula Cannon, USC; Dr. David Hardy, Calimmune; Dr. John Zaia, City of Hope; and Dr. Dale Ando, Sangamo BioSciences. The conversation will be moderated by Jeff Sheehy. Jeff is not only the CIRM Board Patient Advocate member for HIV/AIDS, he’s also a long time community activist in the fight against the virus. You can hear Jeff talk about his commitment to the cause in this video.

The event is on Thursday, July 30th from 5.30p to 8.30p and we’re providing food and refreshments. The location is Fiesta Hall, Plummer Park, 7377 Santa Monica Boulevard, West Hollywood, Los Angeles. And, of course, it’s free.

If you are interested in joining us and being part of the discussion please RSVP to: daniel@beingalivela.org or call 323-874-4322.

We look forward to seeing you there.

New tech tool speeds up stem cell research

It’s hard to do a good job if you don’t have the right tools. Now researchers have access to a great new tool that could really help them accelerate their work, a tool its developers say “will revolutionize the way cell biologists develop” stem cell models to test in the lab.

Fluidigm's Castillo system

Fluidigm’s Callisto system

The device is called Callisto™. It was created by Fluidigm thanks to two grants from CIRM. The goal was to develop a device that would allow researchers more control and precision in the ways that they could turn stem cells into different kinds of cell. This is often a long, labor-intensive process requiring round-the-clock maintenance of the cells to get them to make the desired transformation.

Callisto changes that. The device has 32 chambers, giving researchers more control over the conditions that cells are stored in, even allowing them to create different environmental conditions for different groups of cells. All with much less human intervention.

Lila Collins, Ph.D., the CIRM Science Officer who has worked closely with Fluidigm on this project over the years, says this system has some big advantages over the past:

“Creating the optimal conditions for reprogramming, stem cell culture and stem cells has historically been a tedious and manually laborious task. This system allows a user to more efficiently test a variety of cellular stimuli at various times without having to stay tied to the bench. Once the chip is set up in the instrument, the user can go off and do other things.”

Having a machine that is faster and easier to use is not the only advantage Callisto offers, it also gives researchers the ability to systematically and simultaneously test different combinations of factors, to see which ones are most effective at changing stem cells into different kinds of cell. And once they know which combinations work best they can use Callisto to reproduce them time after time. That consistency means researchers in different parts of the world can create cells under exactly the same conditions, so that results from one study will more readily support and reflect results from another.

In a news release about Callisto,  Fluidigm’s President and CEO Gajus Worthington, says this could be tremendously useful in developing new therapies:

“Fluidigm aims to enable important research that would otherwise be impractical. The Callisto system incorporates some of our finest microfluidic technology to date, and will allow researchers to quickly and easily create complex cell culture environments. This in turn can help reveal how stems cells make fate decisions. Callisto makes challenging applications, such as cellular reprogramming and analysis, more accessible to a wide range of scientists. We believe this will move biological discovery forward significantly.”

And as Collins points out, Callisto doesn’t just do this on a bulk level, working with millions of cells at a time, the way the current methods do:

“Using a bulk method it’s possible that one might miss an important event in the mixture. The technology in this system allows the user to stimulate and study individual cells. In this way, one could measure changes in small sub-populations and find ways to increase or decrease them.”

Having the right tools doesn’t always mean you are going to succeed, but it certainly makes it a lot easier.

Using your own tumor to fight skin cancer

Some things never get old. Like watching the sunset over the Grand Canyon. Listening to a baby laugh. Watching the San Francisco Giants win the baseball World Series. Now you can add to that list learning that one of the clinical trials we are funding has just treated their first patient.

shutterstock_85468885The latest to join that growing list is Caladrius Biosciences (previously called NeoStem). We recently awarded them $17.7 million to carry out a Phase 3 metastatic melanoma clinical trial targeting cancer stem cells. These cells are believed to be able to survive chemotherapy and other cancer-targeting treatments, and can cause a relapse by enabling tumors to grow and spread.

Caladrius’ approach is a personalized one. They use the patient’s own tumor cells to create a therapeutic vaccine called (for now at least) CLBS20. It’s designed to engage the patient’s own immune system and destroy the cancer.

This first patient was treated at Thomas Jefferson University Hospital in Philadelphia. Altogether Caladrius hopes to enroll some 250 patients at more than 40 sites worldwide, for the trial. Seven of those sites are here in California; that’s the portion of the project we are funding.

Because this is a randomized, double blind study it’s not known if the patient was treated with CLBS20 or a placebo. But in a news release Dr. David J. Mazzo, CEO of Caladrius Biosciences, says it’s a big first step:

“The dosing of the first patient in this Phase 3 trial is an important milestone for our Company and the timing underscores our focus on this program and our commitment to impeccable trial execution. We are delighted by the enthusiasm and productivity of the team at Jefferson University and other trial sites around the country and look forward to translating that into optimized patient enrollment and a rapid completion of the Phase 3 trial.”

In the earlier Phase 2 trial, 72 percent of those who got the therapy were still alive after two years, compared to 31 percent of people who got a placebo therapy. There was another bonus for patients; the treatment was well-tolerated with few side effects, the most common being irritation and a reaction at the site of the injection.

There’s a big need for this approach. In 2014 there were approximately 20,000 new cases of metastatic melanoma and nearly 10,000 deaths. It usually causes death within one to two years and only 10 to 15 percent of patients survive five years.

Here’s where to go if you would like more information on the Intus Study or you can also visit the NIH clinical trials site.

Help us chart a new direction

It’s hard to get where you want to go without a map. Even if you have a pretty good idea of where you are heading it’s all too easy to get sidetracked or take a wrong turn. Having a good map helps you stay on course.

Charting a course for success

Charting a course for success

That’s why we are creating our own map, to help us reach our goal, of accelerating stem cell therapies to patients with unmet medical needs.

We’re putting together a new Strategic Plan, something that will help shape our future as we head into our second decade. The idea is simple, how can we best use the money we have left (almost one billion dollars) and all our other resources.

To do that we’re asking the usual suspects for their thoughts and ideas, but we’re also asking some unusual suspects, in fact, we’re asking anyone who is interested to help us develop the plan.

As our President and CEO, Dr. C. Randal Mills, said in a news release LINK:

“No one has a monopoly on good ideas, that’s why we want to hear from a diverse group of people, scientists and non-scientists alike, to learn what they think about how we should best use our money, resources, and expertise to reach our goal. This new Strategic Plan will help create a clear vision for how we move forward, one that sets priorities and an actionable approach to accomplish our mission.”

Anyone wishing to add their voice to those helping us develop the plan can take the online anonymous survey. The deadline is the end of the day Friday, June 26th.

YOU CAN FIND THE SURVEY HERE

As the Chair of our governing Board, Jonathan Thomas, Ph.D., J.D., says:

“We are a state agency. We were created by the people of California and we answer to the people of California. It makes sense that for something this important, a Strategic Plan that will help shape our future for years to come, that we ask the people of California for their thoughts and suggestions.”

Science is filled with uncertainty. Even the most promising therapeutic approach can take a wrong turn. Having a clear road map, a well thought out Strategic Plan, is no guarantee of success, but it certainly means we’ll have a much better idea of how to get where we want to go.

New stem cell could unlock key to colon cancer

One of the fascinating things about stem cell research is how quickly the field is evolving. It seems like every other day a new study is published that highlights a new discovery that makes us stop and think how this new knowledge affects our understanding of stem cells and the diseases we are trying to treat.

The latest example came this week with research from Canada identifying a new kind of stem cell population found in the colon that can lead to cancer growth.

shutterstock_280962560The study, published in the journal Cell Stem Cell,  is important because colon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer death in both men and women, claiming around 50,000 lives in the U.S. alone every year.

Stem cells are essential for helping replace the lining of our colon and intestine every three or four days. In the intestine there are two kinds of stem cells, a rapidly recycling one called Lgr5+ and a slower one. However, scientists had only been able to identify Lgr5+ stem cells in the colon. Because this stem cell type is sensitive to radiation physicians believed that radiation therapy would be effective against colon cancer.

Now, researchers at Lawson Health Research Institute in Ontario, Canada, have identified another stem cell in the colon, one that is both long-lived and radiation resistant.

They also found that this new stem cell population can not only give rise to tumors in the colon, it can also help sustain and support the growth of the cancer.

In a news release Dr. Samuel Asfaha, a clinician-scientist at Lawson and the lead author of the study, says this new piece of information gives them vital new information in fighting the cancer:

 “The identification of more than one stem cell pool in the colon has proven challenging. These findings are exciting, as we have identified an important new target for cancer therapy. It is also proof that more than one stem cell can give rise to and sustain tumors, telling us that our cancer therapy needs to target more than one stem cell pool.”

Asfaha says knowing that there is a pool of stem cells that don’t respond to radiation means researchers must now look for new, more effective ways of tackling them, so we are better able to help patients with colon cancer.

CIRM is funding a number of therapies that target solid tumor cancers, the kind that includes colon cancer. One, run by Dr. Dennis Slamon of University College, Los Angeles, is now in clinical trials. You can read about that work here.

Do patient advocacy groups and pharmaceutical companies need marriage counseling?

A new study suggests that the relationship between patient advocacy groups and pharmaceutical companies, particularly those carrying out clinical trials, is hitting a bit of a rough patch. And that could have big consequences for both parties.

Working together to make a clinical trial succeed

Working together to make a clinical trial succeed

In the past, patients and patient advocacy groups were very much an afterthought when it came to planning clinical trials. Many times they were only brought in to the discussion when pharmaceutical companies had a product they wanted to market or when researchers needed help recruiting patients. Today it’s quite different. Many patient advocate groups are more closely connected with those behind the clinical trials, offering support and advice in helping shape those trials.

Now a report from InVentiv Health, a provider of drug development services for the global pharmaceutical market, suggests that relationship might be experiencing some tension.

Heather Gartman, the regional managing director of InVentiv Health, talked about the report in an interview on Daniel Levine’s *Rare Cast podcast.

“I view the relationship between Patient Advocates and Pharmaceutical companies as similar to a marriage, it’s a good marriage, but like all marriages it has its up and downs.”

InVentiv surveyed more than forty different patient advocacy groups and found that they want to play a bigger role in the way they work with pharmaceutical groups:

  • They want to be involved earlier and play a bigger role in the design and execution of clinical trials.
  • They want greater transparency from their pharmaceutical partners.
  • They want to have a role in the education of patients enrolling in these clinical trials and the physicians involved in deliver the therapies.

Gartman says the patient advocates feel they have a much better understanding of the needs of the patients and so they should be involved right from the start of planning a clinical trial. They believe their early engagement would be helpful in preparing the company for what it needs to do to better serve the patient community, and in particular in helping recruit and retain patients in these clinical trials.

When asked if these groups had unrealistic expectations of companies, who after all are in the business of making money, she said that the patient advocate groups understand that big Pharma is big business, but that by working together they will actually benefit each other, by speeding up the recruitment for and completion of clinical trials and, hopefully, speeding up the delivery of new treatments to patients.

Gartman says she thinks this is just the natural tension that emerges in any relationship but that long-term the “marriage” is strong, with both parties realizing they have too many shared interests to split up.

“It’s a good marriage, all it needs is a little marriage counseling or some small tweaks to help iron out the bumps.”

At CIRM we try to engage the patient advocate right from the start. Under CIRM 2.0, our new way of funding research, as soon as a company or researcher is approved for funding for a clinical trial we set up a Clinical Advisory Panel or CAP. This consists of one of our Science Officers, an outside expert in stem cell research, and a patient advocate. The role of the CAP is to help guide, advise and counsel the research team at every step along the way. We feel it’s important to have the voice of the patient involved right from the start because they have the most at stake here and they bring a unique perspective to the work.

* RARECast is a weekly series by Daniel S. Levine. Levine is an award-winning business journalist who has reported on the life sciences, economic development, and business policy issues throughout his 25-year career. He founded Levine Media Group in 2013, which produces The Bio Report and RARECast podcasts.

How one strong ARM can create a community

I spent the last two days at the annual Washington meeting of the Alliance for Regenerative Medicine (ARM), the advocacy organization that CIRM became a founding member of in 2009. Having been CIRM’s representative at that first organizing meeting it has been a pleasure to see the organization mature into an effective advocacy group for our field. It has lived up to its goal of creating a community where all the stakeholders in the field, from academic and industry leaders to patient advocates and investors, can come together in a coordinated front.

ARM and CIRM share the goal of accelerating the development of regenerative therapies to patients with unmet medical needs. The organization also dovetails well with our effort to inform the public about the great hope in the field. To quote ARM’s website: “ARM also works to increase public understanding of the field and its potential to transform human healthcare.”

But that transformation can be fostered or impeded by actions in our nation’s capital, both regulatory and legislative, the main thrust of the past two days’ activities.

While the iconic Capitol building is the most recognized footprint of our Congress, it is the House and Senate office buildings that ring three sides of the Capitol where most of the work gets done, like in the Rayburn building, which houses the office of Dianna DeGette, the Colorado congresswoman and champion of regenerative medicine.

While the iconic Capitol building is the most recognized footprint of our Congress, it is the House and Senate office buildings that ring three sides of the Capitol where most of the work gets done, like in the Rayburn building, which houses the office of Dianna DeGette, the Colorado congresswoman and champion of regenerative medicine.

ARM members presented three specific proposals for advancing the field to members of congress and their staffs. These would:

  • Create a center of excellence to develop technical and process standards for regenerative medicine. Not very sexy on the surface, but agreement in advance on what regulators will accept in creating a new product can shave months or years off the development of needed therapies.
  • Create a special pathway within the Food and Drug Administration—much like the one created for orphan diseases—for “Qualified Regenerative Medicine Products (QRMPs). These products would have shown potential to change the course of a disease with currently unmet medical needs and the FDA would be required to meet with their sponsors to discuss expedited review of the product.
  • Advocate for the adoption of a national regenerative medicine strategy that includes federal agency coordination, support for research and regulatory reform to create a clear and predictable pathway that enables quick approval of safe and effective products. To accomplish that ARM has promoted the establishment of a Regenerative Medicine Coordinating Council within the U.S. Department of Health & Human Services.
Jamie Goldfarb with her son Kai and husband Jeff. Photo courtesy Melanoma Research Alliance

Jamie Goldfarb with her son Kai and husband Jeff.
Photo courtesy Melanoma Research Alliance

Jamie Goldfarb, who beat back melanoma with the help of a cell-based immune therapy, made a clear and passionate case for the urgency of making it easier to get these therapies to patients at the ARM member dinner Tuesday night:

“Enhanced awareness for the power of regenerative medicine means a world of difference. It means less suffering, less pain, less fear, less expense, less hardship, less loss. It also means more hope, more determination, more love, more strength for individuals and for society as a whole. Every person in this room and those organizations you represent are improving lives.”

Don Gibbons

Hey, don’t throw out that kidney – I can use it

A new approach to recycling old kidneys

A new approach to recycling old kidneys

Researchers at the Wake Forest Institute for Regenerative Medicine have come up with what may be the ultimate in recycling programs. They want to take old, discarded kidneys and, using stem cells, turn them into healthy, functioning kidneys for transplant patients.

Well, that’s the ultimate goal. They’ve still got a way to go, but they’re off to a good start, as shown in two studies published in the journals Transplantation and CellR4.

Their work has a real sense of urgency to it. In the US in 2014 there were around 17,000 kidney transplants, but the waiting list for a kidney is more than 100,000. Every year around 4,000 people die waiting for a transplant. Many others drop off the list because they are too sick to undergo transplantation. Clearly we need more donor kidneys, but how to get them has been a problem for years.

That’s where the Wake Forest work could come in. They want to use the 2,600 kidneys that are donated every year but have to be thrown away because they are not healthy enough for transplantation.

In a news release accompanying the article Dr. Giuseppe Orlando, M.D., Ph.D., a researcher at Wake Forest, said:

“We believe the two studies we are reporting provide critical information to the booming field of organ bioengineering as it applies to the kidney.”

First the team took a discarded kidney and washed it in a mild detergent to remove all the cells, leaving just a kind of kidney scaffold behind. In one experiment they then seeded the kidney scaffold with stem cells taken from amniotic fluid. Over time the scientists say the cells not only settled onto the scaffold but they also started working the way kidney cells should, secreting chemicals and growth factors that are necessary to create new blood vessels.

In a second experiment the researchers wanted to see if washing away the original kidney cells affected a small section of blood vessels called the glomerulus. These are vital to the kidney’s ability to filter out contaminants. So they injected resin into the scaffold to measure if the glomerulus changed in any way. Orlando says they found that the size, structure and function of the micro-vessels in the glomerulus were all preserved after the washing.

“These results indicate that discarded human kidneys are a suitable platform for engineering replacement kidneys and that when cells are added, the structures behave as an effective and viable biosystem.”

The beauty of this approach is that if it works it might allow researchers to take stem cells from a person with kidney problems, and create a new kidney that would match their own immune system, meaning they wouldn’t have to take powerful anti-rejection medications for the rest of their life.

There is still a long way to go before they know if this approach will work. In the meantime there are tens of thousands of people waiting for a transplant, and not just of kidneys but of livers and hearts and other organs.

That’s where we all can help, by signing up to become an organ donor. You can find out more information by going to the websites like Donate California or to the United Network for Organ Sharing (UNOS).

Researchers aren’t the only ones who can help save a life. We all can play our part.

Stem cell therapy for spinal cord injury back on track

When Geron decided, in 2010, to halt the first ever clinical trial of stem cells for spinal cord injury it was a disappointment to many people, particularly for those with spinal cord injuries (SCI) who were hoping it might help them. But now that therapy is back, and the company behind it this time, Asterias Biotherapeutics, has just treated its first patient.

The patient was dosed at the Shepherd Center in Atlanta, Georgia. This trial participant is the first of 13 patients who will be given escalating doses of up to 20 million AST-OPC1 cells to see if they can benefit patients. Up to 8 centers will be involved in the trial, including some in California.

shutterstock_149508221The AST-OPC1’s are a kind of stem cell called an oligodendrocyte progenitor, which can turn into cells that protect nerves and help insulate their signals, much like the insulation of a bare electric wire. In the trial, these progenitor cells are injected into the injured spine. Earlier animal experiments showed the AST-OPC1 cells helped regenerate nerve tissue at the site of injury.

In a news release Dr. Donald Peck Leslie, the medical director of the Shepherd Center, said the people being treated have essentially lost all sensation and movement below their injury site with severe paralysis of the upper and lower limbs:

“If AST-OPC1 could deliver even modest improvements in motor or sensory function, it would result in significant improvements in quality of life for people with SCI.”

The primary goal of the trial – which CIRM is helping fund – is to make sure this approach is safe; so the first three patients treated will get just 2 million cells. If that first group show no bad side effects then the next five patients will get ten million cells, and the next five after that will get 20 million cells.

For people with spinal cord injuries this is clearly a hopeful development. Last year alone 12,000 people in the U.S. suffered a severe spinal cord injury leaving them completely or partially paralyzed. There is no effective treatment.

For the Asterias team this is also an exciting time. Several of them were with Geron when that first trial was cancelled because the company changed its business strategy. Since then the Asterias team has worked long and hard to get the approach revived. This latest news is a recognition that all that effort is paying off.

Of course this is just the start, and there is a long way to go before we know if this approach, these cells, will provide any lasting benefits to people with spinal cord injuries. But the results from the five people treated with these cells at Geron are encouraging. Follow-up studies on those patients have shown no serious side effects due to the therapy and in four of the five patients, MRI scans have shown that the actual injury site had shrunk.

Pedro Lichtinger, President and CEO of Asterias, was full of praise for those agreeing to get the treatment:

“Individuals with SCI have severe disabilities that can significantly shorten projected lifespan, impact quality of life and result in lifetime costs of care of $3 million to $4 million. We are grateful for the interest of patients with SCI to participate in this program.”

That praise for the people who are getting the therapy is well deserved. They have just experienced a life-changing, traumatic experience and have volunteered to be part of a clinical trial where they may not get any benefit because, at least for this first phase, the number of cells being used is comparatively small.

The people volunteering know that this trial is all about safety. But they also know that without these first steps, without their involvement, there can be no progress. They are, in every sense of the word, pioneers in this research. For that they deserve our recognition, and our gratitude.