Building California’s stem cell research community, from the ground up

For week three of the Month of CIRM, our topic is infrastructure. What is infrastructure? Read on for a big picture overview and then we’ll fill in the details over the course of the week.

When CIRM was created in 2001, our goal was to grow the stem cell research field in California. But to do that, we first had to build some actual buildings. Since then, our infrastructure programs have taken on many different forms, but all have been focused on a single mission – helping accelerate stem cell research to patients with unmet medical needs.
CIRM_Infrastucture-program-iconScreen Shot 2017-10-16 at 10.58.38 AM

In the early 2000’s, stem cell scientists faced a quandary. President George W. Bush had placed limits on how federal funds could be used for embryonic stem cell research. His policy allowed funding of research involving some existing embryonic stem cell lines, but banned research that developed or conducted research on new stem lines.

Many researchers felt the existing lines were not the best quality and could only use them in a limited capacity. But because they were dependent on the government to fund their work, had no alternative but to comply. Scientists who chose to use non-approved lines were unable to use their federally funded labs for stem cell work.

The creation of CIRM changed that. In 2008, CIRM launched its Major Facilities Grant Program. The program had two major goals:

1) To accommodate the growing numbers of stem cell researchers coming in California as a result of CIRM’s grants and funding.

2) To provide new research space that didn’t have to comply with the federal restrictions on stem cell research.

Over the next few years, the program invested $271million to help build 12 new research facilities around California from Sacramento to San Diego. The institutions used CIRM’s funding to leverage and attract an additional $543 million in funds from private donors and institutions to construct and furnish the buildings.

These world-class laboratories gave scientists the research space they needed to work with any kind of stem cell they wanted and develop new potential therapies. It also enabled the institutions to bring together under one roof, all the stem cell researchers, who previously had been scattered across each campus.

One other important benefit was the work these buildings provided for thousands of construction workers at a time of record unemployment in the industry. Here’s a video about the 12 facilities we helped build:

But building physical facilities was just our first foray into developing infrastructure. We were far from finished.

In the early days of stem cell research, many scientists used cells from different sources, created using different methods. This meant it was often hard to compare results from one study to another. So, in 2013 CIRM created an iPSC Repository, a kind of high tech stem cell bank. The repository collected tissue samples from people who have different diseases, turned those samples into high quality stem cell lines – the kind known as induced pluripotent stem cells (iPSC) – and then made those samples available to researchers around the world. This not only gave researchers a powerful resource to use in developing a deeper understanding of different diseases, but because the scientists were all using the same cell lines that meant their findings could be compared to each other.

That same year we also launched a plan to create a new, statewide network of clinics that specialize in using stem cells to treat patients. The goal of the Alpha Stem Cell Clinics Network is to support and accelerate clinical trials for programs funded by the agency, academic researchers or industry. We felt that because stem cell therapies are a completely new way of treating diseases and disorders, we needed a completely new way of delivering treatments in a safe and effective manner.

The network began with three clinics – UC San Diego, UCLA/UC Irvine, and City of Hope – but at our last Board meeting was expanded to five with the addition of UC Davis and UCSF Benioff Children’s Hospital Oakland. This network will help the clinics streamline challenging processes such as enrolling patients, managing regulatory procedures and sharing data and will speed the testing and distribution of experimental stem cell therapies. We will be posting a more detailed blog about how our Alpha Clinics are pushing innovative stem cell treatments tomorrow.

As the field advanced we knew that we had to find a new way to help researchers move their research out of the lab and into clinical trials where they could be tested in people. Many researchers were really good at the science, but had little experience in navigating the complex procedures needed to get the green light from the US Food and Drug Administration (FDA) to test their work in a clinical trial.

So, our Agency created the Translating (TC) and Accelerating Centers (AC). The idea was that the TC would help researchers do all the preclinical testing necessary to apply for permission from the FDA to start a clinical trial. Then the AC would help the researchers set up the trial and actually run it.

In the end, one company, Quintiles IMS, won both awards so we combined the two entities into one, The Stem Cell Center, a kind of one-stop-shopping home to help researchers move the most promising treatments into people.

That’s not the whole story of course – I didn’t even mention the Genomics Initiative – but it’s hard to cram 13 years of history into a short blog. And we’re not done yet. We are always looking for new ways to improve what we do and how we do it. We are a work in progress, and we are determined to make as much progress as possible in the years to come.

Saving Ronnie: Stem Cell & Gene Therapy for Fatal Bubble Baby Disease [Video]

During this second week of the Month of CIRM, we’ve been focusing on the people who are critical to accomplishing our mission to accelerate stem cell treatments to patients with unmet medical needs.

These folks include researchers, like Clive Svendsen and his team at Cedars-Sinai Medical Center who are working tirelessly to develop a stem cell therapy for ALS. My colleague Karen Ring, CIRM’s Social Media and Website Manager, featured Dr. Svendsen and his CIRM-funded clinical trial in Monday’s blog. And yesterday, in recognition of Stem Cell Awareness Day, Kevin McCormack, our Senior Director of Public Communications, blogged about the people within the stem cell community who have made, and continue to make, the day so special.

Today, in a new video, I highlight a brave young patient, Ronnie, and his parents who decided to participate in a CIRM-funded clinical trial run by St. Jude Children’s Research Hospital and UC San Francisco in an attempt to save Ronnie’s life from an often-fatal disease called severe combined immunodeficiency (SCID). This disorder, also known as bubble baby disease, leaves newborns without a functioning immune system which can turn a simple cold into a potentially deadly infection.

Watch this story’s happy ending in the video above.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

Can Stem Cell Therapies Help ALS Patients?

A scientist’s fifteen-year journey to develop a stem cell-based therapy that could one day help ALS patients.

Jan Kaufman

Photo of Clive Svendsen (top left) and Jan & Jeff Kaufman

“Can stem cells help me Clive?”

The sentence appeared slowly on a computer screen, each character separated by a pause while its author searched for the next character using a device controlled by his eye muscle.

The person asking the question was Jeff Kaufman, a Wisconsin man in his 40s completely paralyzed by amyotrophic lateral sclerosis (ALS). On the receiving end was Clive Svendsen, PhD, then a scientist at the University of Wisconsin-Madison, determined to understand how stem cells could help patients like Jeff.

Also known as Lou Gehrig’s disease, ALS is a rapid, aggressive neurodegenerative disease with a two to four-year life expectancy. ALS destroys the nerve cells that send signals from the brain and spinal cord to the muscles that control movement. Denervation, or loss of nerves, causes muscle weakness and atrophy, leaving patients unable to control their own bodies. Currently there are two FDA-approved ALS drugs in the US – riluzole and a new drug called edaravone (Radicava). However, they only slow disease progression in some ALS patients by a few months and there are no effective treatments that stop or cure the disease.

Given this poor prognosis, making ALS the focus of his research career was an easy decision. However, developing a therapeutic strategy was challenging to Svendsen. “The problem with ALS is we don’t know the cause,” he said. “Around 10% of ALS cases are genetic, and we know some of the genes involved, but 90% of cases are sporadic.” He explained that this black box makes it difficult for scientists to know where to start when trying to develop treatments for sporadic ALS cases that have no drug targets.

From Parkinson’s disease to ALS

Svendsen, who moved to Cedars-Sinai in Los Angeles to head the Cedars-Sinai Board of Governors Regenerative Medicine Institute in 2010, has worked on ALS for the past 15 years. Before that, he studied Parkinson’s disease, a long-term neurodegenerative disorder that affects movement, balance and speech. Unlike ALS, Parkinson’s patients have a longer life expectancy and more treatment options that alleviate symptoms of the disease, making their quality of life far better than ALS patients.

Clive Svendsen, PhD, Director, Regenerative Medicine Institute. (Image courtesy of Cedars-Sinai)

“I chose to work on ALS mainly because of the effects it has on ALS families,” explained Svendsen. “Being normal one day, and then becoming rapidly paralyzed was hard to see.”

The transition from Parkinson’s to ALS was not without a scientific reason however. Svendsen was studying how an important growth factor in the brain called Glial Cell Line-Derived Neurotrophic Factor or GDNF could be used to protect dopamine neurons in order to treat Parkinson’s patients. However other research suggested that GDNF was even more effective at protecting motor neurons, the nerve cells destroyed by ALS.

Armed with the knowledge of GDNF’s ability to protect motor neurons, Svendsen and his team developed an experimental stem cell-based therapy that they hoped would treat patients with the sporadic form of ALS. Instead of using stem cells to replace the motor neurons lost to ALS, Svendsen placed his bets on making another cell type in the brain, the astrocyte.

Rooting for the underdog

Astrocytes are the underdog cells of the brain, often overshadowed by neurons that send and receive information from the central nervous system to our bodies. Astrocytes have many important roles, one of the most critical being to support the functions of neurons. In ALS, astrocytes are also affected but in a different way than motor neurons. Instead of dying, ALS astrocytes become dysfunctional and thereby create a toxic environment inhospitable to the motors neurons they are supposed to assist.

Fluorescent microscopy of astrocytes (red) and cell nuclei (blue). Image: Wikipedia.

“While the motor neurons clearly die in ALS, the astrocytes surrounding the motor neurons are also sick,” said Svendsen. “It’s a huge challenge to replace a motor neuron and make it grow a cable all the way to the muscle in an adult human. We couldn’t even get this to work in mice. So, I knew a more realistic strategy would be to replace the sick astrocytes in an ALS patients with fresh, healthy astrocytes. This potentially would have a regenerative effect on the environment around the existing motor neurons.”

The big idea was to combine both GDNF and astrocyte replacement. Svendsen set out to make healthy astrocytes from human brain stem cells that also produce therapeutic doses of GDNF and transplant these cells into the ALS patient spinal cord. Simply giving patients GDNF via pill wouldn’t work because the growth factor is unable to enter the brain or spinal cord tissue where it is needed. The hope, instead, was that the astrocytes would secrete the protective factor that would keep the patients’ motor neurons healthy and alive.

With critical funding from a CIRM Disease Team grant, Svendsen and his colleagues at Cedars-Sinai tested the feasibility of transplanting human brain stem cells (also referred to as neural progenitor cells) that secreted GDNF into a rat model of ALS. Their results were encouraging – the neural progenitor cells successfully developed into astrocytes and secreted GDNF, which collectively protected the rat motor neurons.

Svendsen describes the strategy as “a double whammy”: adding both healthy astrocytes and GDNF secretion to protect the motor neurons. “Replacing astrocytes has the potential to rejuvenate the niche where the motor neurons are. I think that’s a very powerful experimental approach to ALS.”

A fifteen year journey from bench to bedside

With promising preclinical data under his belt, Svendsen and his colleagues, including Robert Baloh, MD, PhD, director of neuromuscular medicine at the Cedars-Sinai Department of Neurology, and neurosurgeon J. Patrick Johnson, MD, designed a clinical trial that would test this experimental therapy in ALS patients. In October 2016, CIRM approved funding for a Phase I/IIa clinical trial assessing the safety of this novel human neural progenitor cell and gene therapy.

Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, and Robert Baloh, MD, PhD, director of neuromuscular medicine in the Cedars-Sinai Department of Neurology, in the lab. Svendsen is the sponsor of a current ALS clinical trial at Cedars-Sinai and the overall director of the program. Baloh is the principal investigator for the clinical trial. (Image courtesy of Cedars-Sinai)

This is a first-in-human study, and as such, the U.S. Food and Drug Administration (FDA) required the team to transplant the cells into only one side of the lumbar spinal cord, which effectively means that only one of the patient’s legs will get the treatment. This will allow for a comparison of the function and progression of ALS in the leg on the treated side of the spinal cord compared with the leg on the untreated side.

The trial was approved to treat a total of 18 patients and started in May 2017.

 Svendsen, who first started working on ALS back in 2002, describes his path to the clinic as a “very long and windy road.” He emphasized that this journey wouldn’t be possible without the hard work of his team, Cedars-Sinai and financial support from CIRM.

“It took ten years of preclinical studies and an enormous amount of work from many different people. Just producing the cells that we’re going to use took three years and a lot of trials and tribulations to make it a clinically viable product. It was really thanks to CIRM’s funding and the support of Cedars-Sinai that we got through it all. Without that kind of infrastructure, I can safely say we wouldn’t be here today.”

This “behind-the-scenes” view of how much time and effort it takes to translate a stem cell therapy from basic research into the clinic isn’t something that the public is often exposed to or aware of. Just as “Rome wasn’t built in a day,” Svendsen stressed that good quality stem cell trials take time, and that it’s important for people know how complicated these trials are.

It’s all about the patients

So, what motivates Svendsen to continue this long and harrowing journey to develop a treatment for ALS? He said the answer is easy. “I’m doing it for the patients,” he explained. “I’m not doing this for the money or glory. I just want to develop something that works for ALS, so we can help these patients.”

Svendsen revisited his story about Jeff Kaufman, a man he befriended at the Wisconsin ALS Chapter in 2003. Jeff had three daughters and a son, a wonderful wife, and was a successful lawyer when he was diagnosed with ALS.

“Jeff had basically everything, and then he was stricken with ALS. I still remember going to his house and he could only move his eyes at that point. He tapped out the words ‘Can stem cells help me Clive?’ on his computer screen. And my heart sank because I knew how much and how long it was going to take. I was very realistic so I said, ‘Yes Jeff, but it’s going to take time and money. And even then, it’s a long shot.’ And he told me to go for it, and that stuck in my brain.”

It’s people like Jeff that make Svendsen get out of bed every morning and doggedly pursue a treatment for ALS. Sadly, Jeff passed away due to complications from ALS in 2010. Svendsen says what Jeff and other patients go through is tragic and unfair.

“There’s a gene that goes along with ALS and it’s called the ‘nice person gene,’” he said. “People with ALS are nice. I can’t explain it, but neurologists would say the same thing. You feel like it’s just not fair that it happens to those people.”

The future of stem cell therapies for ALS

It’s clear from speaking with Svendsen, that he is optimistic about the future of stem cell-based therapies for ALS. Scientists still need to unravel the actual causes of ALS. But the experimental stem cell treatments currently in development, including Svendsen’s, will hopefully prove effective at delaying disease progression and give ALS patients more quality years to live.

In the meantime, what concerns Svendsen is how vulnerable ALS patients are to being misled by unapproved stem cell clinics that claim to have cures. “Unfortunately, there are a lot of charlatans out there, and there are a lot of false claims being made. People feed off the desperation that you have in ALS. It’s not fair, and it’s completely wrong. They’ll mislead patients by saying ‘For $40,000 you can get a cure!’”

Compelling stories of patients cured of knee pain or diseases like ALS with injections of their own adult stem cells pop up in the news daily. Many of these stories refer to unapproved treatments from clinics that don’t provide scientific evidence that these treatments are safe and effective. Svendsen said there are reasonable, research-backed trials that are attempting to use adult stem cells to treat ALS. He commented, “I think it’s hard for the public to wade through all of these options and understand what’s real and what’s not real.”

Svendsen’s advice for ALS patients interested in enrolling in a stem cell trial or trying a new stem cell treatment is to be cautious. If a therapy sounds too good to be true, it probably is, and if it costs a lot of money, it probably isn’t legitimate, he explained.

He also wants patients to understand the reality of the current state of ALS stem cell trials. The approved stem cell trials he is aware of are not at the treatment stage yet.

“If you’re enrolled in a stem cell trial that is funded and reputable, then they will tell you honestly that it’s not a treatment. There is currently no approved treatment using stem cells for ALS,” Svendsen said.

This might seem like discouraging news to patients who don’t have time to wait for these trials to develop into treatments, but Svendsen pointed out that the when he started his research 15 years ago, the field of stem cell research was still in its infancy. A lot has been accomplished in the past decade-and-a-half and with talented scientists dedicated to ALS research like Svendsen, the next 15 years will likely offer new insights into ALS and hopefully stem cell-based treatments for a devastating disease that has no cure.

Svendsen hopes that one day, when someone like Jeff Kaufman asks him “Can stem cells help me Clive?” He’ll be able to say, yes they can, yes they can.

CIRM-Funded Clinical Trials Targeting Blood and Immune Disorders

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Today we are featuring trials in our blood and immune disorders portfolio, specifically focusing on sickle cell disease, HIV/AIDS, severe combined immunodeficiency (SCID, also known as bubble baby disease) and rare disease called chronic granulomatous disease (CGD).

CIRM has funded a total of eight trials targeting these disease areas, all of which are currently active. Check out the infographic below for a list of those trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

CIRM-Funded Clinical Trials Targeting the Heart, Pancreas, and Kidneys

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Today we are featuring trials in our organ systems portfolio, specifically focusing on diseases of the heart/vasculature system, the pancreas and the kidneys.

CIRM has funded a total of nine trials targeting these disease areas, and eight of these trials are currently active. Check out the infographic below for a list of our currently active trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

CIRM-Funded Clinical Trials Targeting Brain and Eye Disorders

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

 This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Our Agency has funded a total of 40 trials since its inception. 23 of these trials were funded after the launch of our Strategic Plan in 2016, bringing us close to the half way point of our goal to fund 50 new clinical trials by 2020.

Today we are featuring CIRM-funded trials in our neurological and eye disorders portfolio.  CIRM has funded a total of nine trials targeting these disease areas, and seven of these trials are currently active. Check out the infographic below for a list of our currently active trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

CIRM-Funded Clinical Trials Targeting Cancers

Welcome to the Month of CIRM!

As we mentioned in last Thursday’s blog, during the month of October we’ll be looking back at what CIRM has done since the agency was created by the people of California back in 2004. To start things off, we’ll be focusing on CIRM-funded clinical trials this week. Supporting clinical trials through our funding and partnership is a critical cornerstone to achieving our mission: to accelerate stem cell treatments to patients with unmet medical needs.

Over the next four days, we will post infographics that summarize CIRM-funded trials focused on therapies for cancer, neurologic disorders, heart and metabolic disease, and blood disorders. Today, we review the nine CIRM-funded clinical trial projects that target cancer. The therapeutic strategies are as varied as the types of cancers the researchers are trying to eradicate. But the common element is developing cutting edge methods to outsmart the cancer cell’s ability to evade standard treatment.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

A month of CIRM: Gauging our progress to plan for our future

Every once in a while, it’s a good idea to take a step back and look at what you’ve done, what you’ve achieved. It’s not about identifying the things that have gone well and patting yourself on the back for them; it’s more a matter of assessing where you started, what your goals were, where you succeeded, where you fell short, and where you want to go in the future.

So during the month of October, we are going to be taking a look back at what CIRM has done in the years since we were created by the people of California in 2004. We want to take stock of what we have done and how that has helped shape the agency we are today, and the agency we hope to be in the future.

Each week we will highlight a different area, starting with a look at the projects we are funding in clinical trials – how after our first ten years we had seventeen projects in clinical trials, and today that number is 35 and counting. We’ll also provide updates on our infrastructure programs like the Alpha Stem Cell Clinics Network and the Stem Cell Center – programs that play a critical role in accelerating the development and delivery of high quality stem cell treatments to patients with unmet medical needs.

Over the course of the next few weeks, we’ll show how the way we work has changed and evolved as the field of stem cell research progressed, and how we have tried to be more responsive both to the needs of researchers and patients.

We’ll also be taking a look at the people who have helped play a key role in shaping us, from the scientists who do the work to the patient advocates who are relentless champions of stem cell research. We’ll even profile some of the unsung heroes here at CIRM.

But even as we look back we’re going to use that to frame our future, to see where we are going. We have some big goals for the next few years – as laid out in our Strategic Plan – and we are working hard to get there. By reflecting on the past, using the experienced gained and lessons learned, we hope to have a much clearer view of what we need to do in the years ahead.

Like any good driver we are focused on what is in front of us; but every once in a while, it’s not a bad idea to take a look in the rearview mirror and see what’s behind you, where you have come from.

During October we’re taking a quick look in our rear view mirror. (photo source)