Salk scientists explain why brain cells are genetically diverse

twin_boys

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.”


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Sneak Peak of our New Blog Series and the 10 Years of iPSCs Cell Symposium

New Blog Series

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Shinya Yamanaka

A decade has passed since Dr. Shinya Yamanaka and his colleagues discovered the Nobel Prize-winning technology called induced pluripotent stem cells (iPSCs). These stem cells can be derived from adult tissue and can develop into any cell type in the body. They are an extremely useful tool to model disease in a dish, screen for new drug therapeutics, and have the potential to replace lost or damaged tissue in humans.

In honor of this amazing scientific discovery, we’re launching a new blog series about iPSCs and their impact on CIRM since we started funding stem cell research in 2007. It will be a four-part series over the course of September ending with a blog highlighting the 10 Years of iPSCs Cell Symposium that will be hosted in Berkeley, CA in late September.

Here are the topics:

  • CIRM jumps on the iPSC bandwagon before it had wheels.
  • Expanding the CIRM iPSC bank, how individuals are making a difference.
  • Spotlight on CIRM-funded iPSC research, interviews with CIRM-funded scientists.
  • What the experts have to say, recap of the 10 Years of iPSCs Cell Symposium.

A Conference Dedicated to 10 Years of iPSCs

slide-2Cell Press is hosting a Symposium on September 25th dedicated to the 10th anniversary of Yamanaka’s iPSC discovery. The symposium is featuring famous scientists in biology, medicine, and industry and is sure to be one of the best stem cell conferences this year. The speakers will cover topics from discovery research to technology development and clinical applications of iPSCs.

More details about the Symposium can be found here.

Here are a few of the talks and events we’re excited about:

  • Keynote by Gladstone’s Shinya Yamanaka: Recent progress in iPSC research and application
  • Panel on ethical considerations for clinical translation of iPSC research
  • Organized run with Shinya Yamanaka (I can finally say that I’ve run with a Nobel Prize winner!)
  • Advances in modeling ALS with iPSCs by Kevin Eggan, Harvard University
  • Cellular reprogramming approaches for cardiovascular disease by Deepak Srivastava, Director of the Roddenberry (named after Star Trek’s Gene Roddenberry) Stem Cell Center at the Gladstone Institutes in San Francisco
  • Keynote by MIT’s Rudolf Jaenisch: Stem cells, iPSCs and the study of human development and disease

CIRM will be attending and covering the conference through our blog and on Twitter (@CIRMnews).

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.

Unlocking the secrets of how stem cells decide what kind of cell they’re going to be

Laszlo Nagy, Ph.D., M.D.

Laszlo Nagy, Ph.D., M.D.: Sanford Burnham Prebys Medical Discovery Institute

Before joining CIRM I thought OCT4 was a date on the calendar. But a new study says it may be a lot closer to a date with destiny, because this study says OCT4 helps determine what kinds of cell a stem cell will become.

Now, before we go any further I should explain for people who have as strong a science background as I do – namely none – that OCT4 is a transcription factor, this is a protein that helps regulate gene activity by turning certain genes on at certain points, and off at others.

The new study, by researches at Sanford Burnham Prebys Medical Discovery Institute (SBP), found that OCT4 plays a critical role in priming genes that cause stem cells to differentiate or change into other kinds of cells.

Why is this important? Well, as we search for new ways of treating a wide variety of different diseases we need to find the most efficient and effective way of turning stem cells into the kind of cells we need to regenerate or replace damaged tissue. By understanding the mechanisms that determine how a stem cell differentiates, we can better understand what we need to do in the lab to generate the specific kinds of cells needed to replace those damaged by, say, heart disease or cancer.

The study, published in the journal Molecular Cell, shows how OCT4 works with other transcription factors, sometimes directing a cell to go in one direction, sometimes in another. For example, it collaborates with a vitamin A (aka retinoic acid) receptor (RAR) to convert a stem cell into a neuronal precursor, a kind of early stage brain cell. However, if OCT4 interacts with another transcription factor called beta-catenin then the stem cell goes in another regulatory direction altogether.

In an interview with PhysOrg News, senior author Laszlo Nagy said this finding could help develop more effective methods for producing specific cell types to be used in therapies:

“Our findings suggest a general principle for how the same differentiation signal induces distinct transitions in various types of cells. Whereas in stem cells, OCT4 recruits the RAR to neuronal genes, in bone marrow cells, another transcription factor would recruit RAR to genes for the granulocyte program. Which factors determine the effects of differentiation signals in bone marrow cells – and other cell types – remains to be determined.”

In a way it’s like programming all the different devices that are attached to your TV at home. If you hit a certain combination of buttons you get to one set of stations, hit another combination and you get to Netflix. Same basic set up, but completely different destinations.

“In a sense, we’ve found the code for stem cells that links the input—signals like vitamin A and Wnt—to the output—cell type. Now we plan to explore whether other transcription factors behave similarly to OCT4—that is, to find the code in more mature cell types.”

 

 

How the Ice Bucket Challenge changed the fight against ALS

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200 people in Boston take the Ice Bucket Challenge: Photo courtesy Forbes

A couple of years ago millions of people did something they probably never thought they would: they dumped a bucket of ice cold water on their head to raise awareness about a disease most of them had probably never heard of, and almost certainly knew very little about.

The disease was ALS, also known as Lou Gehrig’s disease, and the Ice Bucket Challenge was something that went from a fun idea by a supporter of the ALS Association, to a blockbuster $220 million fundraiser. Like any good idea it sparked a backlash with critics accusing it of being a lazy way for people to feel good without actually doing anything, of diverting money from other charities, and even of just wasting water at a time of drought (at least here in California.)

But two years later we can now look back and see if those critics were correct, and if the money raised did make a difference. And the answer, I’m happy to say, is no and yes. In that order.

An article in the New Yorker magazine, by James Surowiecki, takes a look at what has happened since the Ice Bucket Challenge exploded on the scene and it has some good news:

  • Contributions to the ALS Association remain higher than before the Challenge
  • The average age of donors dropped from 50+ to 35
  • The Challenge may have helped spur an increase in overall donations to charity

All this is, of course, excellent news. But there’s an even more important point, which is that the money raised by the Challenge has helped advance ALS research further and faster than ever before.

Barbara Newhouse, the CEO of the ALS Association told Surowiecki:

“The research environment is dramatically different from what it was. We’re seeing research that’s really moving the needle not just on the causes of the disease but also on treatments and therapies.”

As an example Newhouse cites a study, published in Science  last summer, by researchers at Johns Hopkins that helped explain protein clumps found in the brains of people with ALS. Philip Wong, one of the lead authors of the study, says money raised by the Challenge helped make their work possible;

“Without it, we wouldn’t have been able to come out with the studies as quickly as we did. The funding from the ice bucket is just a component of the whole—in part, it facilitated our effort.”

And just this week the ALS Association said funding from the Challenge helped identify a gene connected to the disease.

Having been one of those who took a dunk for science – and we did ours early on, when the Challenge had only raised $4m – it’s nice to know something as silly and simple can have such a profound impact on developing treatments for a deadly disorder.

 

 

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.

 

CIRM-funded stem cell clinical trial for retinitis pigmentosa focuses on next stage

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How retinitis pigmentosa erodes normal vision

The failure rate for clinical trials is depressingly high. A study from Tufts University in 2010  found that for small molecules – the substances that make up more than 90 percent of the drugs on the market today – the odds of getting from a Phase 1 trial to approval by the Food and Drug Administration are just 13 percent. For stem cell therapies the odds are even lower.

That’s why, whenever a stem cell therapy shows good results it’s an encouraging sign, particularly when that therapy is one that we at CIRM are funding. So we were more than a little happy to hear that Dr. Henry Klassen and his team at jCyte and the University of California, Irvine have apparently cleared the first hurdle with their treatment for retinitis pigmentosa (RP).

jCyte has announced that the first nine patients treated for RP have shown no serious side effects, and they are now planning the next phase of their Phase 1/2a safety trial.

In a news release Klassen, the co-founder of jCyte, said:

“We are pleased with the results. Retinitis pigmentosa is an incurable retinal disease that first impacts people’s night vision and then progressively robs them of sight altogether. This is an important milestone in our effort to treat these patients.”

The therapy involves injecting human retinal progenitor cells into one eye to help save the light sensing cells that are destroyed by the disease. This enables the researchers to compare the treated eye with the untreated eye to see if there are any changes or improvements in vision.

So far, the trial has undergone four separate reviews by the Data Safety Monitoring Board (DSMB), an independent group of experts that examines data from trials to ensure they meet all safety standards and that results show patients are not in jeopardy. Results from the first nine people treated are encouraging.

The approach this RP trial is taking has a couple of advantages. Often when transplanting organs or cells from one person into another, the recipient has to undergo some kind of immunosuppression, to stop their body rejecting the transplant. But earlier studies show that transplanting these kinds of progenitor cells into the eye doesn’t appear to cause any immunological response. That means patients in the study don’t have to undergo any immunosuppression. Because of that, the procedure is relatively simple to perform and can be done in a doctor’s office rather than a hospital. For the estimated 1.5 million people worldwide who have RP that could make getting treatment relatively easy.

Of course the big question now is not only was it safe – it appears to be – but does it work? Did any of those people treated experience improvements in their vision? We will share those results with you as soon as the researchers make them available.

Next step for the clinical trial is to recruit more patients, and treat them with a higher number of cells. There’s still a long way to go before we will know if this treatment works, if it either slows down, stops, or better still helps reverse some of the effects of RP. But this is a really encouraging first step.


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