Funding stem cell research targeting a rare and life-threatening disease in children

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Photo courtesy Cystinosis Research Network

If you have never heard of cystinosis you should consider yourself fortunate. It’s a rare condition caused by an inherited genetic mutation. It hits early and it hits hard. Children with cystinosis are usually diagnosed before age 2 and are in end-stage kidney failure by the time they are 9. If that’s not bad enough they also experience damage to their eyes, liver, muscles, pancreas and brain.

The genetic mutation behind the condition results in an amino acid, cystine, accumulating at toxic levels in the body. There’s no cure. There is one approved treatment but it only delays progression of the disease, has some serious side effects of its own, and doesn’t prevent the need for a  kidney transplant.

Researchers at UC San Diego, led by Stephanie Cherqui, think they might have a better approach, one that could offer a single, life-long treatment for the problem. Yesterday the CIRM Board agreed and approved more than $5.2 million for Cherqui and her team to do the pre-clinical testing and work needed to get this potential treatment ready for a clinical trial.

Their goal is to take blood stem cells from people with cystinosis, genetically-modify them and return them to the patient, effectively delivering a healthy, functional gene to the body. The hope is that these genetically-modified blood stem cells will integrate with various body organs and not only replace diseased cells but also rescue them from the disease, making them healthy once again.

In a news release Randy Mills, CIRM’s President and CEO, said orphan diseases like cystinosis may not affect large numbers of people but are no less deserving of research in finding an effective therapy:

“Current treatments are expensive and limited. We want to push beyond and help find a life-long treatment, one that could prevent kidney failure and the need for kidney transplant. In this case, both the need and the science were compelling.”

The beauty of work like this is that, if successful, a one-time treatment could last a lifetime, eliminating or reducing kidney disease and the need for kidney transplantation. But it doesn’t stop there. The lessons learned through research like this might also apply to other inherited multi-organ degenerative disorders.

Asterias’ stem cell clinical trial shows encouraging results for spinal cord injury patients

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Jake Javier; Asterias spinal cord injury clinical trial participant

When researchers are carrying out a clinical trial they have two goals: first, show that it is safe (the old “do no harm” maxim) and second, show it works. One without the other doesn’t do anyone any good in the long run.

A few weeks ago Asterias Biotherapeutics showed that their CIRM-funded stem cell therapy for spinal cord injuries appeared to be safe. Now their data suggests it’s working. And that is a pretty exciting combination.

Asterias announced the news at the annual scientific meeting of the International Spinal Cord Society in Vienna, Austria. These results cover five people who got a transplant of 10 million cells. While the language is muted, the implications are very encouraging:

“While early in the study, with only 4 of the 5 patients in the cohort having reached 90 days after dosing, all patients have shown at least one motor level of improvement so far and the efficacy target of 2 of 5 patients in the cohort achieving two motor levels of improvement on at least one side of their body has already been achieved.”

What does that mean for the people treated? A lot. Remember these are people who qualified for this clinical trial because of an injury that left them pretty much paralyzed from the chest down. Seeing an improvement of two motor levels means they are regaining some use of their arms, hands and fingers, and that means they are regaining the ability to do things like feeding, dressing and bathing themselves. In effect, it is not only improving their quality of life but it is also giving them a chance to lead an independent life.

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Kris Boesen, Asterias clinical trial participant

One of those patients is Kris Boesen who regained the use of his arms and hands after becoming the first patient in this trial to get a transplant of 10 million cells. We blogged about Kris here

Asterias says of the 5 patients who got 10 million cells, 4 are now 90 days out from their transplant. Of those:

  • All four have improved one motor level on at least one side
  • 2 patients have improved two motor levels on one side
  • One has improved two motor levels on both sides

What’s also encouraging is that none of the people treated experienced any serious side effects or adverse events from the transplant or the temporary use of immunosuppressive drugs.

Steve Cartt, CEO of Asterias, was understandably happy with the news and that it allows them to move to the next phase:

“We are quite encouraged by this first look at efficacy results and look forward to reporting six-month efficacy data as planned in January 2017.  We have also just recently been cleared to begin enrolling a new cohort and administering to these new patients a much higher dose of 20 million cells.  We look forward to begin evaluating efficacy results in this higher-dose cohort in the coming months as well.”

People with spinal cord injuries can regain some function spontaneously so no one is yet leaping to the conclusion that all the progress in this trial is due to the stem cells. But to see all of the patients in the 10 million stem cell group do well is at the very least a positive sign. Now the hope is that these folks will continue to do well, and that the next group of people who get a 20 million cell transplant will also see improvements.

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Roman Reed, spinal cord injury patient advocate

While the team at Asterias were being cautiously optimistic, Roman Reed, whose foundation helped fund the early research that led to this clinical trial, was much less subdued in his response. He was positively giddy:

“If one patient only improves out of the five, it can be an outlier, but with everyone improving out of the five this is legit, this is real. Cures are happening!”

 

CIRM’s Randy Mills: New FDA rules for stem cells won’t fix the problem

For the last two days the Food and Drug Administration (FDA) has been holding a hearing in Bethesda, Maryland on new regulations that would tighten control over stem cell treatments. The FDA invited public testimony during the hearing on the regulations that would impact many of the clinics that currently offer unproven therapies

The testimony has been impassioned to say the least. Supporters of the clinics say they offer a valuable service and that patients should be allowed to decide for themselves how they want their own cells to be used. Opponents say the clinics are little more than snake oil sales people, offering bogus, unproven treatments.

One of those presenting was Randy Mills, CIRM’s President and CEO. Randy has been very vocal in the past about the need for the FDA to change the way it regulates stem cell therapies.

In California Healthline Randy explained why he thinks the rules the FDA is proposing will not fix the problem, and may even make it worse:

FDA Must Find A Middle Ground For Sake Of Patients

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Randy Mills

We aren’t happy, as a lot of people aren’t happy, with the proliferation of these stem cell clinics — some of which are probably doing good work. But some are clearly making rather outlandish claims for which there’s no real data. 

There are a couple of conditions coming together to create this storm.

One is that the need is very real. These patients are really struggling. They don’t have alternatives. They’re desperate and they need help. It’s not in the realm of possibility to talk to somebody who is suffering as badly as these patients are and to say, ‘You have to wait a few more decades for the science to catch up.’

On the other hand, we have a regulatory paradigm that only provides two pathways to put a cell therapy onto the market. One pathway is the most intense regulatory requirement anywhere in the world for any product — the biologics license application through the FDA, which takes 10 to 20 years and costs over $1 billion.

The other is through the exemptions the FDA has made, which require absolutely no pre-market approval whatsoever. You can be on the market in days, with no data.

The regulatory burden associated with one is massive and the other is almost nonexistent.

So it’s not at all surprising that we’re seeing a proliferation of these stem cell clinics popping up that are operating under the assumption that they fall under the exemption.

What the FDA is doing now is saying, ‘We’re not happy with this. We’re going to define some terms more narrowly than in the past … and make it more difficult to legally be on the market under the less burdensome regulatory pathway.’

That’s what this meeting is about.

The problem with their strategy is twofold. It doesn’t address the patients, or the need side of the equation. And I don’t think it has a chance of actually working because the FDA will acknowledge that they do not have the resources to enforce these types of regulations at the clinic level.

They would have to be essentially regulating the practice of physicians, which is well beyond their capabilities. Even if they were able to enforce it, it would just drive these patients somewhere else.

We’re advocating for the creation of some middle pathway that would bring essentially unregulated therapies into the regulatory fold, but in a manner which could be complied with.

I would rather know these clinics are being regulated and collecting data than have them operating under the radar screen of the FDA. I would like there to be a formal pre-market review of these therapies before they’re put on the market. I would like there to be safety and efficacy data.

I’m going to try hard to get the FDA to see that just plugging this hole won’t make the problem go away.

Thinking that they’re going to strengthen the regulation and that patients are going to be satisfied that there’s absolutely no chance for help is naive.

There isn’t a lot of evidence to suggest these types of procedures are overly risky. It’s not that they don’t have risk, but everything in medicine does. If you’re a patient who has absolutely no alternative, you’re probably willing to take the chance.

Salk scientists explain why brain cells are genetically diverse

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I’ve always wondered why some sets of genetically identical twins become not so identical later in life. Sometimes they differ in appearance. Other times, one twin is healthy while the other is plagued with a serious disease. These differences can be explained by exposure to different environmental factors over time, but there could also be a genetic explanation involving our brains.

The brain is composed of approximately 100 billion cells called neurons, each with a DNA blueprint that contains instructions that determine the function of these neurons in the brain. Originally it was thought that all cells, including neurons, have the same DNA. But more recently, scientists discovered that the brain is genetically diverse and that neurons within the same brain can have slightly different DNA blueprints, which could give them slightly different functions.

Jumping genes and genetic diversity

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Fred “Rusty” Gage: Photo courtesy Salk Institute

Why and how neurons have differences in their DNA are questions that Salk Institute professor Fred Gage has pursued for more than a decade. In 2005, his lab discovered a mechanism during neural development that causes differences in the DNA of neurons. As a brain stem cell develops into a neuron, long interspersed nuclear elements (L1s), which are small pieces of DNA, copy and paste themselves, seemingly at random, throughout a neuron’s genome.

These elements were originally dubbed “jumping genes” because of their ability to hop around and insert themselves into DNA. It turns out that L1s do more than copy and paste themselves to create changes in DNA, they also can delete chunks of DNA. In a CIRM-funded study published this week in the journal Nature Neuroscience, Gage and colleagues at the Salk Institute reported new insights into L1 activity and how it creates genetic diversity in the brain.

Copy, paste, delete

Gage and his team had clues that L1s can cause DNA deletions in neurons back in 2013. They used a technique called single-cell sequencing to record the sequence of individual neuronal genomes and saw that some of their genomes had large sections of DNA added or missing.

They thought that L1s could be the reason for these insertions and deletions, but didn’t have proof until their current study, which used an improved method to identify areas of the neuronal genome modified by L1s. This method, combined with a computer algorithm that can easily tell the difference between various types of L1 modifications, revealed that areas of the genome with L1s were susceptible to DNA cutting caused by enzymes that home in on the L1 sequences. These breaks in the DNA then cause the observed deletions.

Gage explained their findings in a news release:

“In 2013, we discovered that different neurons within the same brain have various complements of DNA, suggesting that they function slightly differently from each other even within the same person. This recent study reveals a new and surprising form of variation that will help us understand the role of L1s, not only in healthy brains but in those affected by schizophrenia and autism.”

Jennifer Erwin, first author on the study, further elaborated:

“The surprising part was that we thought all L1s could do was insert into new places. But the fact that they’re causing deletions means that they’re affecting the genome in a more significant way,” says Erwin, a staff scientist in Gage’s group.”

Insights into brain disorders

It’s now known that L1s are important for the brain’s genetic diversity, but Gage also believes that L1s could play a role in causing brain disorders like schizophrenia and autism where there is heightened L1 activity in the neurons of these patients. In future work, Gage and his team will study how L1s can cause changes in genes associated with schizophrenia and autism and how these changes can effect brain function and cause disease.

Young man with spinal cord injury regains use of hands and arms after stem cell therapy

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Kris Boesen – Photo courtesy USC

Hope is such a fragile thing. We cling to it in bad times. It offers us a sense that we can bear whatever hardships we are facing today, and that tomorrow will be better.

Kris Boesen knows all about holding on to hope during bad times. On March 6th of this year he was left paralyzed from the neck down after a car accident. Kris and his parents were warned the damage might be permanent.

Kris says at that point, life was pretty bleak:

“I couldn’t drink, couldn’t feed myself, couldn’t text or pretty much do anything, I was basically just existing. I wasn’t living my life, I was existing.”

For Kris and his family hope came in the form of a stem cell clinical trial, run by Asterias Biotherapeutics and funded by CIRM. The Asterias team had already enrolled three patients in the trial, each of whom had 2 million cells transplanted into their necks, primarily to test for safety. In early April Kris became the first patient in the trial to get a transplant of 10 million stem cells.

Within two weeks he began to show signs of improvement, regaining movement and strength in his arms and hands:

“Now I have grip strength and do things like open a bottle of soda and feed myself. Whereas before I was relying on my parents, now after the stem cell therapy I am able to live my life.”

The therapy involves human embryonic stem cells that have been differentiated, or converted, into cells called oligodendrocyte progenitors. These are capable of becoming the kind of cells which help protect nerve cells in the central nervous system, the area damaged in spinal cord injury.

The surgery was performed by Keck Medicine of USC’s Dr. Charles Liu. In a news release about the procedure, he says improvements of the kind Kris has experienced can make a huge difference in someone’s life:

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Dr. Charles Liu, Keck School of Medicine: Photo courtesy USC

“As of 90 days post-treatment, Kris has gained significant improvement in his motor function, up to two spinal cord levels. In Kris’ case, two spinal cord levels means the difference between using your hands to brush your teeth, operate a computer or do other things you wouldn’t otherwise be able to do, so having this level of functional independence cannot be overstated.”

We blogged about this work as recently as last week, when Asterias announced that the trial had passed two important safety hurdles.  But Kris’ story is the first to suggest this treatment might actually be working.

Randy Mills, CIRM’s President & CEO, says:

 “With each patient treated in this clinical trial we learn.  We gain more experience, all of which helps us put into better context the significance of this type of event for all people afflicted with debilitating spinal cord injuries. But let us not lose sight of the individual here.  While each participant in a clinical trial is part of the group, for them success is binary.  They either improve or they do not.  Kris bravely and selflessly volunteered for this clinical trial so that others may benefit from what we learn.  So it is fitting that today we celebrate Kris’ improvements and stop to thank all those participating in clinical trials for their selfless efforts.”

For patient advocates like Roman Reed, this was a moment to celebrate. Roman has been championing stem cell research for years and through his Roman Reed Foundation helped lay the groundwork for the research that led to this clinical trial:

This is clear affirmative affirmation that we are making Medical History!  We were able to give a paralyzed quadriplegic patient back the use of his hands! With only half a clinical dosage. Now this person may hold and grasp his loved ones hands in his own hands because of the actions of our last two decades for medical research for paralysis CURE! CARPE DIEM!”

It’s not unheard of for people with the kind of injury Kris had to make a partial recovery, to regain some use of their arms and hands, so it’s impossible to know right now if the stem cell transplant was the deciding factor.

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Kris at home: photo courtesy USC

Kris’ dad, Rodney, says he doesn’t care how it happened, he’s just delighted it did:

“He’s going to have a life, even if (the progress) stops just this second, and this is what he has, he’s going to have a better life than he would have definitely had before, because there are so many things that this opens up the world for him, he’s going to be able to use his hands.”

Seeing is believing: how some scientists – including two funded by CIRM – are working to help the blind see

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How retinitis pigmentosa destroys vision – new stem cell research may help reverse that

“A pale hue”. For most of us that is a simple description, an observation about color. For Kristin Macdonald it’s a glimpse of the future. In some ways it’s a miracle. Kristin lost her sight to retinitis pigmentosa (RP). For many years she was virtually blind. But now, thanks to a clinical trial funded by CIRM she is starting to see again.

Kristin’s story is one of several examples of restoring sight in an article entitled “Why There’s New Hope About Ending Blindness” in the latest issue of National Geographic.  The article explores different approaches to treating people who were either born without vision or lost their vision due to disease or injury.

Two of those stories feature research that CIRM has funded. One is the work that is helping Kristin. Retinitis pigmentosa is a relatively rare condition that destroys the photoreceptors at the back of the eye, the cells that actually allow us to sense light. The National Geographic piece highlights how a research team at the University of California, Irvine, led by Dr. Henry Klassen, has been working on a way to use stem cells to replace and repair the cells damaged by RP.

“Klassen has spent 30 years studying how to coax progenitor cells—former stem cells that have begun to move toward being specific cell types—into replacing or rehabilitating failed retinal cells. Having successfully used retinal progenitor cells to improve vision in mice, rats, cats, dogs, and pigs, he’s testing a similar treatment in people with advanced retinitis pigmentosa.”

We recently blogged about this work and the fact that this team just passed it’s first major milestone – – showing that in the first nine patients treated none experienced any serious side effects. A Phase 1 clinical trial like this is designed to test for safety, so it usually involves the use of relatively small numbers of cells. The fact that some of those treated, like Kristin, are showing signs of improvement in their vision is quite encouraging. We will be following this work very closely and reporting new results as soon as they are available.

The other CIRM-supported research featured in the article is led by what the writer calls “an eyeball dream team” featuring University of Southern California’s Dr. Mark Humayun, described as “a courteous, efficient, impeccably besuited man.” And it’s true, he is.

The team is developing a stem cell device to help treat age-related macular degeneration, the leading cause of vision loss in the US.

“He and his fellow principal investigator, University of California, Santa Barbara stem cell biologist Dennis Clegg, call it simply a patch. That patch’s chassis, made of the same stuff used to coat wiring for pacemakers and neural implants, is wafer thin, bottle shaped, and the size of a fat grain of rice. Onto this speck Clegg distributes 120,000 cells derived from embryonic stem cells.”

Humayun and Clegg have just started their clinical trial with this work so it is likely going to be some time before we have any results.

These are just two of the many different approaches, using several different methods, to address vision loss. The article is a fascinating read, giving you a sense of how science is transforming people’s lives. It’s also wonderfully written by David Dobbs, including observations like this:

“Neuroscientists love the eye because “it’s the only place you see the brain without drilling a hole,” as one put it to me.”

For a vision of the future, a future that could mean restoring vision to those who have lost it, it’s a terrific read.

 

A look back at the last year – but with our eyes firmly on the future

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CIRM President & CEO Randy Mills doesn’t want “good”, he wants “better”

Better.

With that single word Randy Mills, our President and CEO, starts and ends his letter in our 2015 Annual Report and lays out the simple principle that guides the way we work at CIRM.

Better.

But better what?

“Better infrastructure to translate early stage ideas into groundbreaking clinical trials. Better regulatory practices to advance promising stem cell treatments more efficiently. Better treatments for patients in need.”

“Better” is also the standard everyone at CIRM holds themselves to. Getting better at what we do so we can fulfill our mission of accelerating stem cell treatments to patients with unmet medical needs.

The 2015 Annual Report highlights the achievements of the last year, detailing how we invested $135 million in 47 different projects at all levels of research. How our Board unanimously passed our new Strategic Plan, laying out an ambitious series of goals for the next five years from funding 50 new clinical trials, to creating a new regulatory process for stem cell therapies.

Snapshot of CIRM's 2015 Funding

The report offers a snapshot of where our money has gone this year, and how much we have left. It breaks down what percentage of our funding has gone to different diseases and how much we have spent on administration.

Jonathan Thomas, the Chair of our Board, takes a look back at where we started, 10 years ago, comparing what we did then (16 awards for a total of $12.5 million) to what we are doing today. His conclusion; we’re doing better.

But we still have a long way to go. And we are determined to get even better.

P.S. By the way we are changing the way we do our Annual Report. Our next one will come out on January 1, 2017. We figured it just made sense to take a look back at the last year as soon as the new year begins. It gives you a better (that word again) sense of what we did and where we  are heading. So look out for that, coming sooner than you think.

Dr. Deborah Deas joins CIRM Board

Deborah Deas has been appointed dean of the UCR School of Medicine

Deborah Deas, MD, MPH, UCR School of Medicine

Dr. Deborah Deas is clearly not someone who opts for the quiet life. If she were, she would have stayed home in Adams Run, the tiny town in rural South Carolina where she was born.

The website, NeighborhoodScout.com describes Adams Run (current population 1,492) as:

“One of the quietest neighborhoods in America. When you are here, you will find it to be very quiet. If quiet and peaceful are your cup of tea, you may have found a great place for you.”

Dr. Deas obviously wasn’t a tea drinker because she packed her bags and went off to college in Charleston. That was the first step on a journey that led the self-described “farmer’s daughter” to become an MD, then an MPH (Masters in Public Health), before assuming a leadership role at the Medical University of South Carolina (MUSC). More recently she headed to California’s Inland Empire where she was named the Dean and CEO for Clinical Affairs of the UC Riverside School of Medicine.

And now we are delighted to add to that list of achievements by announcing she is the newest member of the CIRM Board.

She was appointed to the Board by state Treasurer John Chiang who praised her for her:

“Passion to improve  health for underserved populations and to diversify the health care work force. She is committed to making the benefits of advanced medicine available to all Californians.”

 

In a news release our CIRM Board Chair, Jonathan Thomas, was equally fulsome in his praise and welcome to Dr. Deas.

 “We are delighted to have someone with Dr. Deas’ broad experience and expertise join us at CIRM. Her medical background and her commitment to diversity and inclusion are important qualities to bring to a Board that is striving to deliver stem cell treatments to patients, and to reflect the diversity of California.”

To say that she brings a broad array of skills and experience to the Board is something of an understatement. She is board certified in adult psychiatry, child and adolescent psychiatry and addiction psychiatry, and is widely regarded as a national leader in research into youth binge drinking, adolescent nicotine dependence, marijuana use and panic disorder, and pharmaceutical treatment of pediatric depressive disorder.

As if that wasn’t enough, she has also been named as one of the best doctors in the U.S. by U.S. News & World Report for the last eight years.

But the road to UC Riverside and CIRM hasn’t always been easy. In a first person perspective in Psychiatric News.

she said that at MUSC she was just one of two African Americans among the 500 residents in training:

“It was not uncommon for me to be mistaken by many for a social worker, a secretary, or a ward clerk despite wearing my white coat with Deborah Deas, M.D., written on it. This mistake was even made by some of my M.D. peers. I found that the best response was to ask, “And just why do you think I am a social worker?”

She says the lessons she learned from her parents and grandparents helped sustain her:

“They emphasized the importance of setting goals and keeping your eyes on the prize. Service was important, and the ways that one could serve were numerous. The notion that one should learn from others, as well as teach others, was as common as baked bread. My parents instilled in me that education is the key to a fruitful future and that it is something no one can take away from you.”

Her boss at UC Riverside, the Provost and Executive Vice Chancellor, Paul D’Anieri said Dr. Deas is a great addition to the CIRM Board:

“Deborah is a public servant at heart. Her own values and goals to help underserved patient populations align with the goals of CIRM to revolutionize medicine and bring new, innovative treatments to all patients who can benefit. I am confident that Dr. Deas’ service will have a lasting positive impact for CIRM and for the people of California.”

Dr. Deas ends her article in Psychiatric News saying:

“The farmer’s daughter has come a long way. I have stood on the shoulders of many, pushing forward with an abiding faith that there was nothing that I could not accomplish.”

She has indeed come a long way. We look forward to being a part of the next stage of her journey, and to her joining CIRM and bringing that “abiding faith” to our work.

 

 

Stem cell stories that caught our eye: turning on T cells; fixing our brains; progress and trends in stem cells; and one young man’s journey to recover from a devastating injury

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A healthy T cell

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

Directing the creation of T cells. To paraphrase the GOP Presidential nominee, any sane person LOVES, LOVES LOVES their T cells, in a HUGE way, so HUGE. They scamper around the body getting rid of viruses and the tiny cancers we all have in us all the time. A CIRM-funded team at CalTech has worked out the steps our genetic machinery must take to make more of them, a first step in letting physicians turn up the action of our immune systems.

We have known for some time the identity of the genetic switch that is the last, critical step in turning blood stem cells into T cells, but nothing in our body is as simple as a single on-off event. The Caltech team isolated four genetic factors in the path leading to that main switch and, somewhat unsuspected, they found out those four steps had to be activated sequentially, not all at the same time. They discovered the path by engineering mouse cells so that the main T cell switch, Bcl11b, glows under a microscope when it is turned on.

“We identify the contributions of four regulators of Bcl11b, which are all needed for its activation but carry out surprisingly different functions in enabling the gene to be turned on,” said Ellen Rothenberg, the senior author in a university press release picked up by Innovations Report. “It’s interesting–the gene still needs the full quorum of transcription factors, but we now find that it also needs them to work in the right order.”

Video primer on stem cells in the brain.  In conjunction with an article in its August issue, Scientific American posted a video from the Brain Forum in Switzerland of Elena Cattaneo of the University of Milan explaining the basics of adult versus pluripotent stem cells, and in particular how we are thinking about using them to repair diseases in the brain.

The 20-minute talk gives a brief review of pioneers who “stood alone in unmarked territory.” She asks how can stem cells be so powerful; and answers by saying they have lots of secrets and those secrets are what stem cell scientist like her are working to unravel.  She notes stem cells have never seen a brain, but if you show them a few factors they can become specialized nerves. After discussing collaborations in Europe to grow replacement dopamine neurons for Parkinson’s disease, she went on to describe her own effort to do the same thing in Huntington’s disease, but in this case create the striatal nerves lost in that disease.

The video closes with a discussion of how basic stem cell research can answer evolutionary questions, in particular how genetic changes allowed higher organisms to develop more complex nervous systems.

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CIRM Science Officers Kelly Shepard and Kent Fitzgerald

A stem cell review that hits close to home.  IEEE Pulse, a publication for scientists who mix engineering and medicine and biology, had one of their reporters interview two of our colleagues on CIRM’s science team. They asked senior science officers Kelly Shepard and Kent Fitzgerald to reflect on how the stem cell field has progressed based on their experience working to attract top researchers to apply for our grants and watching our panel of outside reviewers select the top 20 to 30 percent of each set of applicants.

One of the biggest changes has been a move from animal stem cell models to work with human stem cells, and because of CIRM’s dedicated and sustained funding through the voter initiative Proposition 71, California scientists have led the way in this change. Kelly described examples of how mouse and human systems are different and having data on human cells has been critical to moving toward therapies.

Kelly and Kent address several technology trends. They note how quickly stem cell scientists have wrapped their arms around the new trendy gene editing technology CRISPR and discuss ways it is being used in the field. They also discuss the important role of our recently developed ability to perform single cell analysis and other technologies like using vessels called exosomes that carry some of the same factors as stem cells without having to go through all the issues around transplanting whole cells.

“We’re really looking to move things from discovery to the clinic. CIRM has laid the foundation by establishing a good understanding of mechanistic biology and how stem cells work and is now taking the knowledge and applying it for the benefit of patients,” Kent said toward the end of the interview.

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Jake Javier and his family

Jake’s story: one young man’s journey to and through a stem cell transplant; As a former TV writer and producer I tend to be quite critical about the way TV news typically covers medical stories. But a recent story on KTVU, the Fox News affiliate here in the San Francisco Bay Area, showed how these stories can be done in a way that balances hope, and accuracy.

Reporter Julie Haener followed the story of Jake Javier – we have blogged about Jake before – a young man who broke his spine and was then given a stem cell transplant as part of the Asterias Biotherapeutics clinical trial that CIRM is funding.

It’s a touching story that highlights the difficulty treating these injuries, but also the hope that stem cell therapies holds out for people like Jake, and of course for his family too.

If you want to see how a TV story can be done well, this is a great example.

CIRM Board targets diabetes and kidney disease with big stem cell research awards

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A recent study  estimated there may be more than 500 million people worldwide who have diabetes. That’s an astounding figure and makes diabetes one of the largest chronic disease epidemics in human history.

One of the most serious consequences of untreated or uncontrolled diabetes is kidney damage. That can lead to fatigue, weakness, confusion, kidney failure and even death. So two decisions taken by the CIRM Board today were good news for anyone already suffering from either diabetes or kidney disease. Or both.

The Board awarded almost $10 million to Humacyte to run a Phase 3 clinical trial of an artificial vein needed by people undergoing hemodialysis – that’s the most common form of dialysis for people with kidney damage. Hemodialysis helps clean out impurities and toxins from the blood. Without it waste will build up in the kidneys with devastating consequences.

The artificial vein is a kind of bioengineered blood vessel. It is implanted in the individual’s arm and, during dialysis, is connected to a machine to move the blood out of the body, through a filter, and then back into the body. The current synthetic version of the vein is effective but is prone to clotting and infections, and has to be removed regularly. All this puts the patient at risk.

Humacyte’s version – called a human acellular vessel or HAV – uses human cells from donated aortas that are then seeded onto a biodegradable scaffold and grown in the lab to form the artificial vein. When fully developed the structure is then “washed” to remove all the cellular tissue, leaving just a collagen tube. That is then implanted in the patient, and their own stem cells grow onto it, essentially turning it into their own tissue.

In earlier studies Humacyte’s HAV was shown to be safer and last longer than current versions. As our President and CEO, Randy Mills, said in a news release, that’s clearly good news for patients:

“This approach has the potential to dramatically improve our ability to care for people with kidney disease. Being able to reduce infections and clotting, and increase the quality of care the hemodialysis patients get could have a significant impact on not just the quality of their life but also the length of it.”

There are currently almost half a million Americans with kidney disease who are on dialysis. Having something that makes life easier, and hopefully safer, for them is a big plus.

The Humacyte trial is looking to enroll around 350 patients at three sites in California; Sacramento, Long Beach and Irvine.

While not all people with diabetes are on dialysis, they all need help maintaining healthy blood sugar levels, particularly people with type 1 diabetes. That’s where the $3.9 million awarded to ViaCyte comes in.

We’re already funding a clinical trial with ViaCyte  using an implantable delivery system containing stem cell-derived cells that is designed to measure blood flow, detect when blood sugar is low, then secrete insulin to restore it to a healthy level.

This new program uses a similar device, called a PEC-Direct. Unlike the current clinical trial version, the PEC-Direct allows the patient’s blood vessels to directly connect, or vasularize, with the cells inside it. ViaCyte believes this will allow for a more robust engraftment of the stem cell-derived cells inside it and that those cells will be better able to produce the insulin the body needs.

Because it allows direct vascularization it means that people who get the delivery system  will also need to get chronic immune suppression to stop their body’s immune system attacking it. For that reason it will be used to treat patients with type 1 diabetes that are at high risk for acute complications such as severe hypoglycemic (low blood sugar) events associated with hypoglycemia unawareness syndrome.

In a news release Paul Laikind, Ph.D., President and CEO of ViaCyte, said this approach could help patients most at risk.

“This high-risk patient population is the same population that would be eligible for cadaver islet transplants, a procedure that can be highly effective but suffers from a severe lack of donor material. We believe PEC-Direct could overcome the limitations of islet transplant by providing an unlimited supply of cells, manufactured under cGMP conditions, and a safer, more optimal route of administration.”

The Board also approved more than $13.6 million in awards under our Discovery program. You can see the winners here.