Friday, August 31, 2012

Finding a therapy for macular degeneration

One thing about working at CIRM is that you meet a lot of amazing people living with a lot of disease that are all in need of cures.

One of those people I’ve met is Virginia Knepper-Doyle, who has the most common cause of blindness in older people called macular degeneration. We went to her home near Tiburon, just outside San Francisco, to film her as part of a video on stem cell therapies for macular degeneration. She’s an artist, and as her vision grew worse her paintings became more abstract, and in my opinion more lovely. Judges apparently agree with me because she has been invited to participate in more art shows since she began losing her vision.

Knepper-Doyle is featured in a story in the San Francisco Chronicle this week. Writer Erin Allday summed up progress toward treating macular degeneration, including implants, new drugs, and of course stem cells.

She quotes CIRM science officer Ingrid Caras:
"As our population is aging, the number of people affected is going to grow. And you have people who are otherwise healthy but they can't read, they can't drive - that's a huge burden on society," said Ingrid Caras, a science officer at the California Institute for Regenerative Medicine, which has pumped about $50 million into funding for stem cell research to treat macular degeneration.
"Macular degeneration is very high on the priority list of diseases that need attention," Caras said.
We have more information on our website about CIRM projects to develop stem cell-based therapies for macular degeneration (you can see that here). That page also has a list and description of all the awards.

One of our macular degeneration awards is a $15 million disease team that hopes to start clinical trials soon. They’ve found a way of maturing embryonic stem cells into the cells at the back of the eye that degrade in people with macular degeneration. In animals, the researchers can slide sheets of those cells into the back of the eye where they appear to help the animals regain vision. We have a more detailed description of that work, along with a slideshow of Knepper-Doyle’s paintings, on our website.

The company Advanced Cell Technology also has a clinical trial underway testing a different form of stem cell therapy for macular degeneration. Whichever therapy proves most effective—whether it’s the implants Allday describes, new drugs or a stem cell approach—it’s a disease that demands a therapy.

Here's the video that includes our conversation with Virginia Knepper Doyle


Wednesday, August 29, 2012

HIV/AIDS advocate Jeff Sheehy reappointed to CIRM's governing board

Lieutenant Governor Gavin Newsom, Jeff Sheehy and CIRM governing board chair Jonathan Thomas
You find out the most unexpected things in announcements from state bodies. For instance, a recent news release from State Senate President pro Tempore Darrell Steinberg’s office contained this line: Charles J. Sheehy, a Democrat from San Francisco, has been reappointed as a representative of an HIV/AIDS advocacy group to the California Institute for Regenerative Medicine Independent Citizens Oversight Committee.

I’ve known Mr. Sheehy for many years, dating back to my time as a TV journalist specializing in health and medical news, but I had no idea his given first name was Charles! Who knew? Everyone I know calls him Jeff. But while I didn’t know his first name, what I do know about Jeff is that he is a tireless advocate for patients and that we are delighted he has signed up for another tour of duty as a member of our governing board.

In his day job Jeff is the Director for Communications at the AIDS Research Institute at UCSF. He is also a longtime HIV/AIDS and gay civil rights activist and a person living with HIV. He brings with him not just a wealth of experience but also a great deal of compassion and dedication, all wonderful qualities to have in someone who plays such an important role in shaping how we do our job.

But his most important role is in helping keep us focused on what our real purpose is here, namely, finding treatments for people with chronic diseases and disorders. Jeff never loses sight of that goal and his impact is felt at every level of our organization. For example, there are seven subcommittees on the ICOC, our governing board, and Jeff is a member and very active participant on six and is Co-Chair on one of them, the Science Subcommittee. (There's more about the subcommittees on our website.)

In many ways Jeff embodies one of the founding principals of CIRM: that patient advocates have a voice in everything we do, help shape the way we work, and the research we fund. But he is also a lot more than that. He is a great colleague to have around – particularly for those of us who work in communications. He always has good ideas and brings a fresh perspective to any conversation. And he’s always happy to help out in any way he can. For a small organization with huge goals, that’s always appreciated.

His involvement extends to blogging for us – he’s written in the past about our HIV/AIDS projects and about the involvement of patient advocates in funding decisions. You can read can read those posts here. He also worked with us on a video that discusses the HIV/AIDS project led by John Zaia at City of Hope.

Jeff was sworn in this week by Lieutenant Governor Gavin Newsom and his term runs till November 30, 2020. Which is great news for us. Jeff is blessed with a sharp mind and an open heart, and we consider ourselves fortunate he is going to continue to be an important part of our work for at least the next 8 years.


Tuesday, August 28, 2012

Stem cell trial for autism: hope vs. caution

Last week brought a media and social media frenzy over the announcement that a new clinical trial would be testing the effect of injecting cord blood into kids with autism.

The trial—and the conversation surrounding it—illustrates a tension in stem cell science between the hope of the patients and caution on the part of scientists.

What’s important to remember is that this is just a trial. Often, I see new trials heralded as proof that stem cells are working, especially by those who really want to believe in that trial. New trials testing adult versions of stem cells, for example, are heralded as proof of the effectiveness of adult stem cells compared to their embryonic counterparts.

A trial is just that—a trial. More early stage clinical trials fail than succeed. That’s how science moves forward. Right now it’s easier to get a trial started with adult stem cells than with embryonic stem cells, and so there are many more of them. But trials don’t equal success.

Given that this trial may or may not provide any relief for kids with autism or their parents, it’s too soon to be celebrating.

Scientist and science writer Emily Willingham has written about her concerns regarding the science behind this trial. She characterizes the excitement as “stem cells are hot and autism is hot so lets throw some stem cells at autism.” Her blog entry is worth a read. In it, she discusses her concerns about the scientific rational for using cord blood as a therapy for autism.

However, a person commenting on Willingham’s blog makes exactly the point we often struggle with at CIRM. That is, when is it the right time to take risks. The commenter Chris August notes, “As a parent with a child with mild Autism I cheer progress.” He goes on to make the point that even if the stem cells aren’t a magic wand, there’s no harm in testing them. (Willingham herself has a child with autism, which she mentions in her response.)

In a story in Nature’s blog, the lead investigator of the trial Michael Chez gives his own reason for why it’s important to be testing blood cells for autism even if the science behind the trial isn’t strong. Cord blood cells and fat stem cells are being administered overseas as a possible treatment for autism.
“Our research is important because many people are going to foreign countries and spending a lot of money on therapy that may not be valid.”
He’s right. CIRM is one of many organizations and individuals who are worried about the rise of stem cell tourism, in which unregulated clinics overseas promise miracle cures at a steep cost (here's information on our website about stem cell tourism). Those miracle cures are often based on shaky science, or have no scientific basis at all. They aren’t part of clinical trials and outcomes aren’t recorded. At least in the case of this trial, people who participate will be followed and any benefit or lack thereof will be recorded and could help guide future trials.

On our own governing board this tension between funding the very best science and taking risks to push the science forward for life-threatening diseases comes up routinely. Our patient advocate board members, who make up 10 of the 29 members, sometimes push for funding for science that didn’t get the highest scores from our scientific reviewers. Their point: maybe it’s not a sure thing, but it might help us learn something important.


Monday, August 27, 2012

Alan Trounson: The path from IVF scientist to international stem cell advocate

CIRM president Alan Trounson was one of the early scientists working to help women get pregnant through in vitro fertilization. His team was responsible for the eight of the first 10 IVF babies born in Australia. Five million babies have now been born worldwide using the technique.

Trounson’s work in that field is what led him to stem cell science. The technique mixes sperm and egg in a lab dish to develop embryos that can be implanted into a woman’s uterus. Left over embryos from IVF are the source for human embryonic stem cells.

In a story in Western Australia Today, Trouson talks about applying what he learned earlier in his career to his role leading CIRM. Most importantly, patience.
''Like with 5 million babies, it takes a good 25 years to embed into society that this science may be a good thing. It takes a long time for clinical trials - often it's seven to nine years before research gets to be put to use in general medicine.''
Since coming to CIRM in 2008, Trounson has been a strong advocate for building international teams of researchers. The agency now has agreements with 20 international funding agencies, U.S. states and foundations which have contributed to 25 CIRM-funded projects. (You can read more about those collaborations on our website.)
''I am a global scientist, sort of a facilitator, trying to get the world's best scientists to not only work together but work with health authorities and institutes in various countries,'' Trounson says. ''This combined effort is making stem-cell research more effective globally, and it's possibly unique in the area of medical research.''
In the WAToday piece, Trouson pointed to HIV, diabetes, brain tumors, leukemia, forms of blindness and heart disease as areas where projects funded by the agency could soon be entering clinical trials.

A related story profiles Trounson’s oldest daughter Kylie, who is a playwrite. In that story she recounts how she came to understand IVF research, which was highly controversial at the time.
''My experience of IVF was being four years old and not allowed to answer the home phone because it could be right-to-lifers calling with threats against Dad, or people going through our rubbish, or driving past the old convent on St Georges Road just after I'd learned to read and reading out 'Alan Trounson is a baby murderer' to my mum, who's driving and going, 'Oh god, why did I teach this kid to read so early?' ''
She has written a play about those early days of IVF research. Trounson urged her to make the women entering IVF trials the heros of the play.
“They were the truly selfless people in this picture; they went through all of this, didn't get a baby of their own but really felt that they had contributed to the science.''


Friday, August 24, 2012

The waiting ends: Federal funding of embryonic stem cell research deemed legal

Good news today regarding stem cell litigation that had put federal funding of embryonic stem cell research in jeopardy. Three judges on federal appeals court upheld a lower court’s July 2011 ruling that dismissed the lawsuit.

The lawsuit sought to prevent federal funding for human embryonic stem cell research, claiming that the research violated the Dickey-Wicker amendment that prohibits federal funding of research in which human embryos are destroyed.

The Dickey-Wicker amendment does prevent federal funding for the creation of human embryonic stem cell lines, which uses embryos left over from in vitro fertilization clinics. These 4-5 day old embryos are the source of virtually all human embryonic stem cell lines in use today.

However, federal agencies such as the National Institutes of Health – the major funder of biomedical research in the United States – have been able to fund research using human embryonic stem cell lines. Under president Bush, the number of lines that were available for federal funding was severely restricted. Under president Obama, many additional lines became available for federal funding once they had passed an ethics review. A registry of all lines approved for federal funding is available here.

CIRM has been able to fund the creation of new stem cell lines, several of which are also included on the NIH registry, and additional lines are listed here. Our Stem Cell Basics includes information about how new stem cell lines are created.

The judges for the U.S. Court of Appeals for the District of Columbia Circuit wrote three different rationales for their decision but were unanimous in the key decision, writing:
Because we conclude that the district court committed no error, we affirm the order and judgment under review.
Here's some history on the lawsuit from this blog:

Thursday, August 23, 2012

Stem Cell Awareness Day 10/3/12 - what are you doing to spread the word?

Visitors tour stem cell research labs at Sanford-Burnham Medical Research  Institute
What are you doing October 3? If your answer doesn’t have something to do with stem cell events, it’s time to start planning. That date marks the fifth annual Stem Cell Awareness Day, an international effort to educate people about the field of stem cell research. You can learn more about the day on the website:

Last year, Stem Cell Awareness Day brought 31 events in four U.S. states and seven countries. Those events ranged from public lectures to opportunities for people to tour stem cell labs and meet some of the patients who could benefit from stem cell research.

Each year CIRM also encourages stem cell scientists to visit high school classes and talk about their research. Last year, scientists spoke with more than 1,000 students throughout California.

We’ll be updating the Events section of the Stem Cell Awareness Day website as we learn about events being hosted throughout California or in other states or countries. If you don’t see events at an institution near you, we encourage you to contact the institution and let them know that you’d like to attend a public lecture. Better yet, offer to help put something together or ask a researcher to visit your patient advocacy group.

Researchers who are interested in visiting classrooms or participating in public events should contact Don Gibbons

We have more information on our website about how you can get involved in stem cell awareness throughout the year. That information is on our Get Involved page.


Tuesday, August 21, 2012

Partnering event helps move research into therapies

The Alliance for Regenerative Medicine is once again collaborating with CIRM on a Partnering Forum associated with the annual Stem Cell Meeting on the Mesa in La Jolla. According to their press release:
This forum provides a unique opportunity within the regenerative medicine field to facilitate translational research, encourage PI engagement with the business community, and provide the opportunity for hundreds of business, academic research and investor participants to connect for one-on-one meetings and strategic partnering.
Admittedly, talking about “strategic partnering” doesn’t have the same feel-good vibe as talking about new cures, but the two are intertwined. Many of the projects CIRM funds are going to need help from investors and industry to take their research through clinical trials and to patients. Events like this one bring together great research and potential investors and it’s those relationships that will bring the new cures.

The meeting is still a ways off – it doesn’t start until October 29 – but you can see preliminary speaker lists and attendees at the web site:


Friday, August 17, 2012

CIRM fosters new industry

CIRM funding spawns patch technology company to treat blindness

We’ve written a lot in the past year about our increased efforts to engage with industry and to connect our researchers with industry partners. In most cases, we need the involvement of biotechnology and pharmaceutical companies if the research by our grantees is going to reach patients. Those companies are the ones that will take the therapy candidates and move them through clinical trial and into the clinic.

Given our focus on industry it was nice to see a story in today’s Science-Business Exchange, which is a joint publication of BioCentury and Nature. The story requires a paid subscription to read. The story points out that in addition to funding one company in the most recent round of funding, two companies have resulted from the first round of Disease Teams:
Moreover, 2 of those 12 projects have spawned new companies: in 2011 the City of Hope brain cancer project leader founded TheraBiologics Inc., and also in 2011 the University of Southern California (USC) age-related macular degeneration (AMD) project team spun out Regenerative Patch Technologies Inc.
Generating new companies based on CIRM-funded research creates new jobs in the state, which is one of CIRM’s goals.

It’s hard to predict which research will be most successful. However, the story does quote CIRM’s Don Gibbons talking about which disease team projects are closest to reaching clinical trials.
Gibbons declined to say which of the 2009 projects might reach the clinic first but added that CIRM president Alan Trounson “has indicated he thinks the HIV team at City of Hope and the macular degeneration team of USC are pretty close.”


Thursday, August 16, 2012

Where are our projects on the path to the clinic? Find out

Phases of the therapy development pipeline

I’ve been spending time recently updating CIRM’s website to reflect all the new awards that came out of last month’s Disease Team funding. About a year ago, when I first posted sections to the website showing our projects that are headed toward disease therapies I could see the entire list without scrolling. Try that now:

Here’s a link to our therapy-focused projects online.

We now have 71 projects worth more than $530 million all working toward disease therapies. Some of these are at the earliest stages—trying to show that their idea for a therapy has potential. Other projects, like ones for melanoma, osteoporosis, ALS (Lou Gehrig’s disease), Huntington’s disease, vascular disease and SCID (“bubble boy disease”) all intend to complete at least one phase of testing their therapy in clinical trials in the next four years.

As I go through and add the new projects to the list, I can’t help but think of all the patient advocates I’ve met during my time at CIRM who have spoken so passionately for funding in their disease area. For almost every disease category, there is a person I’ve met who either has the disease or who is caring for a family member with that disease. We don’t have cures yet, but I do like seeing all the promising therapies coming down the pipeline.

For people with an interest in a specific disease, you can go to our disease pages and see all the projects focused on that disease area. The pages also have all of our videos that focus on that disease. In therapy development jargon, the group of projects that are working toward therapies is called a therapy development portfolio.

You can see that portfolio on our website, and also download documents we’ve created as handouts to explain our funding strategy. (Those PDFs are at the top of the page.)


Tuesday, August 14, 2012

High school students gain experience, get excited about stem cell research

High school student Brandon Hernandez discusses his summer research at the Creativity Awards meeting
One of the things that’s fun about working at CIRM is knowing that we are making a real difference in people’s lives. We got to see evidence of that yesterday when a group of 63 high school students and their mentors from throughout California got together on Stanford campus to share the results of their summer research as part of our Creativity Awards program. (We blogged about the program here.)

This program supports high school students from all socioeconomic backgrounds doing research projects in stem cell labs. The goal is to foster an interest in stem cell biology in the state’s most promising young people.

And promising they were. These students had more poise while giving talks and discussing their research than many graduate students I’ve known—and I heard a few explaining their research in multiple languages. What could be more representative of California’s diversity and high tech prowess than young people speaking in multiple languages about stem cell research discoveries?

Among the many impressive students I met was Brandon Hernandez, who has been doing research at Scripps Research Institute in La Jolla. The San Diego Union Tribune recently profiled Hernandez. He has been on his own since he was 13, and is now giving talks about medical research and has plans to attend UC Berkeley.

Students like Hernandez and all the other bright young people at the meeting yesterday make me hopeful for our state’s future. These kids are going places.

Irv Weissman, who directs Stanford's stem cell institute, spoke to the students about how he started his career in stem cell research, and about the promise of the field.


Monday, August 13, 2012

Newly discovered brain stem cell could aid in therapies for Alzheimer's, autism

Ulrich Mueller, Ph.D., is a professor and director of the Dorris Neuroscience Center at the Scripps Research Institute.
Scientists at Scripps Research Institute in La Jolla have found a previously unknown type of stem cell in the brain. This one forms the nerves that make up the outer layers of the brain – those layers called the cortex that specifically carry out our higher reasoning.

Until now, the thinking had been that all of the brain’s cells come from a single group of stem cells. This distinction could prove important for developing therapies based on stem cells. Whether a therapy is attempting to inject new stem cells into the brain or manipulate the cells that are already there, the scientists need to know that they are working with the right stem cell.

A press release from Scripps talks about how the work could be important and quotes lead author Ulrich Mueller. The team’s work was published on Aug. 10 in the journal Science.
Up until now, researchers trying to reproduce human cortical neurons in the lab from stem cells have only generated lower-layer-type neurons. "This opens a door now to try to make the upper-layer neurons, which are frequently affected in psychiatric disorders," said Mueller.
Studies like this one highlight how much there is still to learn about how stem cells build our bodies during development and maintain organs as adults. Developing stem cell-based therapies isn’t a matter of just injecting a stem cell into the damaged organ and hoping for the best. Scientists need to use the right kind of stem cell for each task.

When we interviewed Lawrence Goldstein about Alzheimer’s disease recently he had a great analogy for why scientists can’t just inject any old stem cell into the brain as a “cure” for disease. He pointed out that an iPhone’s mechanics are made of metal, but if your iPhone breaks, you don’t just inject a bunch of metal into the phone. You have to open it up and put the right kind of metal in the right places to fix the specific problem.

This study from Scripps brings scientists one step closer to knowing which is the right kind of metal (or stem cell) to fix disorders like Alzheimer’s disease and autism, which involve the outer brain regions that arise from the newly identified stem cells.

CIRM funding: Santos Franco (TG2-01165)


ResearchBlogging.orgSantos J. Franco, Cristina Gil-Sanz, Isabel Martinez-Garay, Ana Espinosa, Sarah R. Harkins-Perry, Cynthia Ramos, and Ulrich Müller (2012). Fate-Restricted Neural Progenitors in the Mammalian Cerebral Cortex Science DOI:

Friday, August 10, 2012

Video: Stem Cell Research Funding = Hope for Huntington’s Patient Advocates

When we produced our first Huntington’s disease (HD) video two years ago, I was really taken in by the close bonds between those living with the disease and the stem cell researchers looking for a treatment. The feelings of mutual respect, admiration, and friendship were very palpable. They spoke of each other as if they were family. I’ve come to learn that this bond has a lot to do with the fact that Huntington’s is a family disease.

A child of a parent with HD has a 50 percent risk of developing this neurodegenerative disorder which typically strikes in a person's thirties and leads to death about 10 to 15 years later. With no effective therapy for the disease, the individual families affected by HD have banded together as one big family for support and to advocate for a cure. And in the process they’ve welcomed the stem cell researchers as one of their own.

Several members of this Huntington’s community were in town two weeks ago with confetti, hugs, and bittersweet tears to celebrate the CIRM governing board’s approval of a $19 million UC Davis Huntington’s Disease Team II grant. The two minute video above captures the excitement of the moment (you can also view it here). Judy Roberson, a patient advocate whose husband died of HD, explained the importance of the award:
This disease team award for the first time in history - we have a chance to make a difference for a treatment for Huntington’s disease.
The UC Davis team led by Vicki Wheelock and Jan Nolta, plans to use bone marrow derived mesenchymal stem cells to deliver a growth factor to patients’ damaged and endangered nerves. The factor they have chosen, called BDNF, has been shown to be effective in laboratory studies in reducing nerve cell death and improving the function of nerves. During this project they will finalize laboratory tests and begin a phase 1 clinical trial in patients to test the safety of the approach. Although Dr. Wheelock’s team was the recipient of the grant, her focus at the meeting was on the entire HD community:
This gives hope to the families who have been suffering with this dreadful disease without any meaningful treatment to halt it or to slow it down.
This grant was one of eight Disease Team II awards approved by the governing board which total $150 million in new research funding (Read our earlier blog here and the press release here). Claire Pomeroy, a CIRM board member and Dean of the UC Davis School of Medicine, reflected on the big picture of this new CIRM award:
I think it is the epitome of what Proposition 71 hoped which was scientists and patients coming together to find hope.

Thursday, August 9, 2012

High school students find summer excitement in stem cell labs

The Los Angeles area’s largest National Public Radio station, KPCC, aired a great piece this morning on a group of local teens who gave up a summer at the beach for a summer of 40-hour weeks in stem cell labs at the Broad Center at the University of Southern California. They also did a print version of the story and both are available on the station’s web site.

Ten of the students in the USC program are part of the CIRM Creativity initiative that has 65 high school students in stem cell labs at nine universities and hospitals this summer. A smaller pilot of that program was so successful last summer that we announced the rollout of a larger initiative in March (read the press release here)

Just as CIRM places an emphasis on funding the full pipeline of stem cell research, we also value educating future stem cell scientists at all points on the educational pipeline. Kathryn Rich, director of training and educational programs at USC’s Broad Center makes that point in the KPCC piece:
We’re all very excited for the potential of stem cell and regenerative medicine and what it can do for human health. Training the next generation is a key part of that.
In addition to these summer opportunities for teens, CIRM has worked with a team at UC Berkeley to develop a five-unit on-line high school curriculum on stem cells that is available free to teachers anywhere.

The 40-hour weeks inside in a lab offer a sharp contrast to the popular view of LA teens frolicking at a beach. Rich said that most of the students love science so much that work in the lab becomes a lifestyle. One student, Sophie McCallister, agreed in the KPCC piece:
This is one of the great spots for looking into regenerative medicine and stem cells in general. I couldn’t have asked for anything more to do with my summer.
Sixty-three of the CIRM summer interns will be presenting posters on their research projects at a symposium at Stanford on Monday (August 13). We filmed some of the teens at last year’s symposium, which captured one of the better feel good moments of working at CIRM. Special thanks to CIRM colleague Mani Vessal who organizes the program.


Monday, August 6, 2012

The heart of cancer: Cancer stem cells shown to exist in three tumors

Back in 1994, a Canadian researcher named John Dick made a cancer discovery that kicked off what has been an 18 year debate. He found that for people with a certain kind of leukemia—called acute myelogenous leukemia—a small group of slow-dividing cells seem to be the source of all the other cancer cells. If a chemotherapy doesn’t eradicate these cells, which he called cancer stem cells, then the cancer will come back.

After his discovery in leukemia, groups including several CIRM grantees at Stanford University and UCLA started finding cancer stem cells in other forms of leukemia and, controversially, in solid tumors. Now that controversy seems to be over.

Three papers published last week in the journals Science and Nature show the presence of cancer stem cells in cancers of the brain, intestines and skin. The L.A. Times quotes CIRM grantee and cancer stem cell expert Owen Witte of UCLA:
"People can stop arguing. Now they can say, 'OK, the cells are here. We now need to know how to treat them.'”
CIRM had bet that cancer stem cells exist, investing heavily in research projects intending to find therapies for cancer that eradicate the cancer stem cells. One of those projects, led by UC San Diego scientist Catriona Jamieson, has already resulted in a clinical trial for a form of pre-leukemia. You can see a list of all CIRM cancer awards here.

Most cancer therapies destroy the fast-growing cells that make up the bulk of the disease. If the more slowly-dividing cancer stem cells survive that treatment, then the cancer will return. By showing that the cancer stem cells do exist scientists can focus their efforts on finding was of eradicating that very different population of cells.

This story from Stanford University has more background about the history of cancer stem cells.

Here is Catriona Jamieson describing cancer stem cells back in 2008.


Friday, August 3, 2012

Guest blogger Alan Trounson — July’s stem cell research highlights

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

Of the six papers I discuss in this month’s full report, I just want to highlight two here. Both combine cell therapy with gene therapy to produce results that suggests the approach can reverse the damage of disease, at least in animal models.

This work is important to me and to California’s stem cell agency because I, and many of my colleagues, believe that this combination of gene therapy and cell therapy will produce some of the most dramatic results in regenerative medicine. In 2009 when we issued our first round of Disease Team awards five of 14 involved this combo. All of our disease teams have the goal of getting to a clinical trial within four years. Last week, in our second round of Disease Team grants, half of the eight grants awarded so far involved gene therapy with stem cells. The press release describing those awards is here. These therapies fall neatly into CIRM’s niche; they have high potential impact and they would be difficult to fund through normal channels. Such approaches, known as “dual modality” therapies, require passing through two different regulatory channels at the Food and Drug Administration, and this scares off many traditional investors.

The first paper discussed Huntington’s disease (HD) work at the CIRM-funded Buck Institute in Novato (although we did not fund this particular project). The team there started with iPS cells, in this case made by reprogramming skin cells from Huntington’s patients that had been made previously by another team. Then they replaced the defective Huntington gene with a correct copy using a clever technique that involves an artificial bacteria chromosome. When they matured those gene-corrected stem cells into the type of nerve cells destroyed in HD and transplanted those cells into a mouse model of the disease, they saw nerves grow that seemed to function normally.

The second paper involves work with muscular dystrophy (MD) done jointly at University College London and the San Rafaele Institute in Milan. They too, began with iPS cells, ones they created from the skin of patients with a specific form of MD called limb-girdle muscular dystrophy. They developed a way to push those stem cells to become large quantities of the precursor cells that can become muscle. Then they corrected the gene that is mutated in LGMD using a virus to carry the new gene into the cells. When they injected those cells into mice with a form of the disease, the cells homed to the damaged muscle and formed new muscle fibers.

A few of our disease teams have similarly produced early data in animal models suggesting their gene-therapy-plus-stem-cell combinations can correct disease in animal models (we blogged about some of that work in HIV/AIDS here). Collectively these results make us feel good that we may be going down a path that will be productive and help eliminate suffering caused by many diseases. My colleague blogged about the most recent Disease Team awards here.

My full report is available online, along with links to my reports from previous months.


Thursday, August 2, 2012

Needle in a haystack search turns up compound that might mend broken hearts

Stem cell-derived heart muscle cells 
The first task of developing a stem cell-based therapy is coaxing the stem cells to turn into the desired cell type – neurons for brain diseases, pancreatic cells for diabetes, or, in the case of some recent work by a group of CIRM grantees, heart muscle cells for heart disease.

A group of researchers from Sanford-Burnham and Human BioMolecular Research Institute in San Diego screened 17,000 compounds to find one that would push embryonic stem cells from mice to form heart tissue. They published the results of that screen--which produced one compound that could push stem cells to form heart tissue--today in the journal Cell Stem Cell.

A press release from Sanford-Burnham quotes researcher Mark Mercola, who is director of Sanford-Burnham’s Muscle Development and Regeneration Program and senior author of the study:
“Heart disease is the leading cause of death in this country. Because we can’t replace lost cardiac muscle, the condition irreversibly leads to a decline in heart function and ultimately death. The only way to effectively replace lost heart muscle cells—called cardiomyocytes—is to transplant the entire heart. Using a drug to create new heart muscle from stem cells would be far more appealing than heart transplantation.”
The way scientists go about screening all these compounds is essentially a high-tech method of extracting a needle from a molecular haystack. They put embryonic stem cells within small indents on lab plates, each of which had 384 such indents called wells. Then, using a robot arm to automate the process, they put a different compound in each of the wells. The stem cells then bathed in those different compounds for a few days. Some of the compounds killed the cells outright, while others nudged the cells to begin forming different kinds of tissues. Since the goal of this particular screen was to find those cells that had begun to form heart tissue, the scientists had engineered the cells to turn green when a gene involved in heart formation was active. When the group ran those plates through a special sensor a few days later, all they had to do was look for wells containing green cells. They found one such group of cells, corresponding to one of the compounds.

The group is now working with San Diego biotech company ChemRegen to turn the compound into a drug that could be used to repair damaged heart tissue.

Here's a video Sanford-Burnham produced about the work:

CIRM Funding: Erik Willems (T2-00004), John Cashman (RS1-00169-1), Mark Mercola (RC1-00132)


ResearchBlogging.orgErik Willems, Joaquim Cabral-Teixeira, Dennis Schade, Wenqing Cai, Patrick Reeves, Paul J. Bushway, Marion Lanier, Christopher Walsh, Tomas Kirchhausen, Juan Carlos Izpisua Belmonte, John Cashman, & Mark Mercola (2012). Small Molecule-Mediated TGF-β Type II Receptor Degradation Promotes Cardiomyogenesis in Embryonic Stem Cells Cell Stem Cell DOI: 10.1016/j.stem.2012.04.025