Guest blogger Alan Trounson — May’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.

I devote most of my report this month to four papers that report significant progress in regenerating the two tissues that make up the bulk of our bodies, bone and muscle. In the past, both have been difficult to grow from stem cells in sufficient quantities to be therapeutically useful.

Two teams grew bone in the lab, one from stem cells found in fat and one from cells derived from embryonic stem cells. Both found that the lab-grown bone grew and matured when transplanted into mice. Two other teams got sufficient muscle regeneration to treat mice with a disease that mimics muscular dystrophy. One started with muscle precursor cells derived from pluripotent stem cells. The other found a protein that could summons naturally occurring putative stem cells called satellite cells and get them to regenerate muscle. (We blogged about those muscle regeneration papers here and here.)

However, the most important of the papers I highlighted this month may be the two that delve into the issue of aging stem cells. We have adult stem cells in most, if not all, the tissues of our bodies that throughout our life get called out of their stem cell niches—sort of store rooms—to make repairs and replace those tissues. Much of the break down of various tissues and loss of organ function that comes with aging is caused by a loss in number of stem cells, or a loss of them to fully function. This has lead many to question whether we can put new stem cells into an aging environment and expect them to do the work we want them to do.

One team this month reported that they had verified the role of a specific protein in the loss of function in blood-forming stem cells. They also showed that a drug-like compound could block the action of that protein and restore old stem cells to functioning like young ones. The other team, mapped a series of signals that start with a molecule sent from the niche cells that result in decreased numbers of stem cells, in at least one setting. They were able to block that pathway and get increased numbers of stem cells.

Both papers reinforce the need to be mindful of the impact of aging on stem cells, but also point to ways to bypass this obstacle. Good news.

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

A.T.

New stem cell awards bring therapies closer to patients

At last week’s board meeting we funded 21 new awards worth $69 million. These were the third round of our recurring Early Translational Awards. (Here’s our press release about those awards.)

Going into that governing board meeting, board member Leeza Gibbons wrote about what supporting new research awards means to her:

“Every time we consider applications for funding, I confess to getting almost breathless. The very thought that we might be setting into motion the cure for a disease which could save millions of lives is the thrill of a lifetime. I’m always excited to vote for great science to unlock the mystery of Alzheimer’s disease. At every meeting, I think of my grandmother and my mother, both of whom died of the disease. It makes me feel better to know I can honor them by funding hope for the future, and I can tell the families I work with who are so desperate for answers, that they are coming. We’re closer than we’ve ever been.”

The goal of these awards is to fund a stage of research in which scientists take a finding that they’ve discovered in their basic research and investigate whether that drug or cell type is as promising as it first seems—whether it really has potential as a new therapy.

In this chart showing the stages of research leading up to clinical trials, the Early Translational Awards support projects in the first two categories: finding proof of concept and identifying a development candidate. Our Disease Team awards support the final stage leading up to a clinical trial.

We have more information about the stages of therapy development on our website.

The awards we funded last week bring the total number of projects in those three stages of the therapy development pipeline to 63. (Those projects are on our website.) Some of the newly funded projects are in disease areas we’ve funded before, like Alzheimer’s disease. Others are investigating disease areas that hadn’t been represented before like SCID (bubble boy disease) and Danon disease. We also significantly upped our commitment to heart disease, funding four additional projects for this devastating condition. You can see descriptions of all the awards on our website.

A.A.

With stem cell tourism getting closer to home know the “ISSCR facts”

Over the past few years the stem cell research community has become increasingly concerned that the actions of overseas clinics offering unproven therapies would taint the field as a whole. The International Society for Stem Cell Research has been particularly active in monitoring this phenomenon and has set up a special web site to help inform the public: A closer look at stem cell treatments.

Internet searches have long turned up scores of off shore clinics offering therapies for numerous diseases, usually not specifying what the actual cell therapy is. They generally provide only anecdotal testimony of any therapeutic benefit, and no long-term data showing what percent of their patients’ conditions improved and that the improvement lasted over time. Recently these internet searches turned up similar looking clinics making similar claims, but based here in the U.S.

An article in yesterday’s Sarasota Herald-Tribune details a reporter’s effort to answer a query from a desperate woman wanting advice about a Florida clinic she was considering taking her husband to for therapy for his chronic obstructive pulmonary disease. The reporter directed to the woman to the ISSCR web site but also provided a nice summary of the organization’s “Top 10 Stem Cell Treatment Facts.”

Here are a couple of “facts” I consider most critical for patients to consider:

2. A single stem cell treatment will not work on a multitude of unrelated diseases or conditions.

4. Just because people say stem cells helped them doesn’t mean they did.

9. An experimental treatment offered for sale is not the same as a clinical trial.

The Herald-Tribune article offers more detail on each fact. We also provide more information on the topic on our web site. We co-hosted a public symposium on proper clinical trials with ISSCR in 2010 when the organization’s annual meeting was in San Francisco. A video of that presentation is also available on our site.

We also produced this video with CIRM grantee and Scripps faculty member Jeanne Loring discussing her concerns about stem cell tourism.

D.G.

Meeting Huntington’s disease advocates drives search for a cure

Emily Krull died from Huntington’s disease when she was 21

There’s nothing quite like getting out and meeting the people affected by some of the diseases we are working to cure to make you feel both humble and privileged.

Humble, because you appreciate how awful these diseases are and the toll they take on individuals and their families and loved ones, as well as the courage and determination they display every single day in working to overcome these problems.

Privileged, because you feel so fortunate to be part of the effort to find therapies to help treat these diseases.

This past weekend I was fortunate enough to be at the Team Hope Walk, the annual fund and awareness-raising event put on by the Huntington’s Disease Society of America – Orange County chapter, at UC Irvine.

They had probably close to 600 people show up to run, walk, or stroll with their dogs. Many did so in honor of someone they know, and they wore badges with pictures of the loved one, putting a face on this horrible disease. But there was nothing sad or downbeat about the event, instead it was a celebration. A celebration of life, of love, of hope and of the drive to find a cure.

Looking into the eyes of someone who has Huntington’s, or talking to the parents of a child who has died from the juvenile version of the disease, you can’t help but be moved.

It makes the work we do at the stem cell agency much more personal. It’s not about abstract ideas or concepts; it’s about people. People like Emily Krull.

Emily, who had Juvenile Huntington’s, died when she was just 21, but her spirit lives on in her parents, Ted and Carla, who helped organize the Team Hope Walk. Carla says Emily is with them in everything they do, and it’s her spirit who helps keep them going.

And it’s their spirit, and stories like theirs, that help keep us going.

This page has a list of California’s stem cell agency grants focused on Huntington’s disease. Watch our video to learn more about one stem cell approach to treating the disease.

K.M.

San Francisco man cured of HIV, CIRM teams replicating the success

San Francisco Magazine has a long story today featuring Timothy Ray Brown—otherwise known as the Berlin patient—who is the first person to be HIV-positive but is now completely free of the virus. His treatment came in the form of a bone marrow transplant, which two projects funded by California’s stem cell agency are now working to replicate.

It’s a remarkable story and the reporter quotes CIRM board member Jeff Sheehy talking about meetings leading up to CIRM’s funding about whether there was even a need for a cure.

“One reviewer said, ‘The science is great, but there’s no need because patients are doing great. They’re happy with antiretroviral drugs,’” recalls Sheehy, who is also communications director for UCSF’s AIDS Research Institute. “That’s when I said, ‘No.’”

Sheehy told the committee that today’s HIV drugs, which he’s been taking since 1997, are far from a total solution. At best, they turn HIV/AIDS into a chronic condition that requires lifetime therapy, at a cost of around $20,000 a year. The drugs can have significant side effects, including bone, kidney, and liver damage. People living with HIV are also more prone to cancer, heart disease, cognitive problems, and a host of other conditions. (A recent study suggests that having HIV may cut a person’s life expectancy by 13 years.)

“I lose friends every year to cancer or heart disease,” Sheehy told his audience. “That wouldn’t be happening if they weren’t infected.’’ As the father of
a seven-year-old daughter, Sheehy worries that HIV might have the same effect on him.

The story goes on to describe the science behind Brown’s cure and CIRM’s approach to replicating it. You can read summaries of the two projects at UCLA and City of Hope on our website. We’ve also blogged about the progress those teams are making toward their goal of reaching clinical trials.

Last year we talked to Sheehy about living with HIV infection and his hope for a cure:

A.A.

Bringing patient advocates into decisions about new therapies

When it comes to scientific research one of the most important voices, that of the patient or patient advocate, has often been one of the hardest to hear. But that is changing and CIRM is not only helping lead the way but also helping shape how, when and where those voices are heard. (Our board member Jeff Sheehy has blogged about this effort.)

Traditionally patients, patient advocates or lay members of the public were brought into the development of new drugs or therapies or technology towards the end of the process. Even then there was often just one or two members of the public on a large scientific panel and their role was frequently limited to approving or rejecting a new product or therapy. This had the effect of ensuring that the group which had the most to gain from the research often had the least to say about it.

In recent decades patient activists – such as people with HIV/AIDS or breast cancer – have demanded a bigger role in research. When CIRM was created Proposition 71 specifically called for 10 of the 29 members of the governing board to be patient advocates. (A list of those members is available on our website.)

The idea was to have their voices heard earlier on in the debate when they could have a bigger say in shaping the direction the research takes, to put the patient at the center of the research, and to increase trust in the process.

But while few would argue that patients and the public don’t deserve a place at the table there are many questions about how big a role they should play, and how they should be chosen.

To try and answer some of those questions a two-day working group meeting was held in Washington DC earlier this year. Hosted by the Hastings Center, a bioethics research institute, the meeting brought together 20 representatives from the FDA, patient advocacy groups, industry and health policy scholars. CIRM’s Senior VP of R&D Ellen Feigal and board member Duane Roth were also part of the conversation.

There were a lot of issues to cover such as how to balance the need for more voices without creating a huge, unwieldy body; the need for those voices to be informed and able to add something to the discussion and not just defer to the scientific experts; the need to understand how representative a patient representative is and will they report back to their community; the need for scientists and industry to accept and appreciate the enhanced role of the public in the process.

While the workshop posed more questions than it provided answers the overall conclusion was that greater participation by the public in research was important. The attendees came up with a series of recommendations including encouraging the FDA to undertake a greater outreach to identify a broader range of stakeholders, to develop new mechanisms for public input, and to provide training to both scientists and the public on how to work together.

The workshop was an important step in the process. The next step is for Hastings to write a paper on the discussion and move the debate to a wider audience. That paper is expected to be available later this year.

Clearly there is a lot of work to be done to turn these ideas into reality, but the workshop showed the growing acceptance of the vital role of patients and the public in the scientific review process; that it is no longer enough just to give them a seat at the table, they also need to have a voice.

K.M.

Gaining stem cell research experience, changing lives

If it seems like we write a lot about our Bridges trainees, it’s because they keep doing interesting things. These students, mostly from community colleges and California State University campuses, get opportunities to take classes in stem cell biology and carry out research in stem cell labs at partner institutions.

Sarah Imam, a CSUN Bridges student, with UCLA stem cell researcher Dr. Michael Teitell (courtesy of Kim Irwin)

Recently UCLA wrote about Sarah Imam, from CSU Northridge, who has been doing research in the lab of CIRM grantee Michael Teitall at UCLA. The story quotes CSUN’s Bridges program director Cindy Malone:

“The Bridges students are exposed to projects and experiences that we can’t provide to them here under any circumstances,” said Malone, who teaches and runs a lab at CSUN. “We don’t have the kind of research facilities or the resources that UCLA has. This program offers students the whole environment of being immersed in a research career.”

Imam said that she had wanted to go to medical school. After her internship she now wants to pursue research as well with an M.D., Ph.D. She said:

“My experience in the Bridges program has changed my perspective. I see research now as an indispensable element to medicine, and it’s exciting to think of a future contributing to solutions to challenging medical conditions.”

She’s not alone in having her career interests altered by the program. I had the opportunity to meet a former Bridges student Benjamin Parcher who was visiting CIRM’s vice chair Senator Art Torres (retired).

Parcher’s experience in the Bridges program influenced his decision to enter a Doctor of Pharmacy program at UCSF. His exposure to research that could benefit people led him to a career where he could interact with patients directly. He said, “I aim to work with patients who need or are receiving regenerative therapies of the type CIRM fosters in clinical investigation settings. Thus, a role that is hands on and research based.”

These kinds of stories show the importance of exposing young people to research that could improve human health. They are now qualified for careers in fields where their experience and expertise can lead to new therapies and better patient care.

Here is more information about the Bridges program and a map of the participating institutions. This video gives some background on the types of projects undertaken by the Bridges students:

A.A.

Assemblymember Nancy Skinner: CIRM to Adopt Public Access Policy for Publications

By Assemblymember Nancy Skinner (D-Berkeley)

Assemblymember Nancy Skinner (D-Berkeley)

For a person struggling with a life-altering diagnosis, the click of a button can connect patients and their families to cutting edge research.

Coupled with the advice of a doctor, access to online libraries such as PubMedCentral, which provides access to federally-funded biomedical research, can provide patients and their families with various long-term treatment options and can empower them to make educated health decisions.

Since 2006, the California Institute for Regenerative Medicine has funded innovative research in the areas of Alzheimer’s disease, autism and leukemia, to name a few. Until now, the publications containing the results of this research have not generally been available to the public. And even though CIRM requires grant recipients to submit a 500 word summary of their research, neither the publications nor the summaries are currently available on CIRM’s website.

Earlier this year, I discussed with the CIRM Governing Board my intentions to bring forward legislation to make their groundbreaking research available to the public. As a result of those conversations, the CIRM board unanimously voted on March 21, 2012 to develop an open access policy. This week, the Board will transmit the regulation to the Office of Administrative Law, initiating a public comment period prior to final adoption of the rule.

It is worth remembering that 2004’s Proposition 71 California Stem Cell Research and Cures Act, the initiative creating CIRM, passed with over 59% of the vote and that that the initiative to authorize $3 billion for stem cell research was, and remains, entirely novel: direct public funding of specific scientific research. At the time, researchers and the public were frustrated by the Bush Administration’s actions to restrict stem cell research. Proposition 71 posited that it was in the best interest of the State of California to fund research that may help find cures to multiple sclerosis, diabetes, and other diseases.

Since its passage, scientists at academic institutions and industries have used CIRM’s funding to pursue original and important research into stem cell therapies. Their results have been published in prestigious peer-reviewed publications, bringing potential stem cell therapies closer to reality.

In the words of CIRM Board Member Joan Samuelson, Californians are “funding the research and results” and are eager to see the benefits and potential of stem cell research. Access to publications is one way to demonstrate CIRM’s value to the public funders.

Similar open access policies have already been in place for researchers funded by the National Institutes of Health – or NIH. Since 2008, the NIH open access policy has required NIH-funded researchers to make their peer-reviewed papers available for free on www.PubMedCentral.gov. With PubMed Central, millions of researchers, industry, and the general public are able to directly access information about diseases, empowering them to understand sometimes deeply personal issues. This searchable library of federally-funded biomedical research is a wonderful demonstration of how to improve access to our most valuable public resource: knowledge.

Our experience with PubMedCentral demonstrates that the benefits of a public access policy are tremendous, while the downsides and arguments against such a policy are overstated. Such policies also provide a way to improve accountability for publicly-funded programs like CIRM. The proposal for CIRM’s new policy mirrors the NIH’s open access policy, and even if it’s a bit overdue, it’s a good step toward transparency and will make CIRM-funded research even more valuable to the people of California.

Assemblymember Nancy Skinner represents the fourteenth Assembly District, which includes Albany, Berkeley, Canyon, East Richmond Heights, El Cerrito, El Sobrante (part), Emeryville, Kensington, Lafayette, Moraga, Oakland (part), Orinda, Pleasant Hill, Richmond, Rollingwood, San Pablo, and Waldon (part).

Gene found to activate muscle stem cells in mice with muscular dystrophy

Julie Saba grew up with a father who was a muscle biochemist and, out of rebellion, she swore she’d never go into research, especially muscle research. She was just going to be a doctor. A doctor who, years later, did run a research lab, but in cancer.

Then, when studying a particularly interesting gene involved in cancer biology, she discovered that fruit flies lacking the gene couldn’t fly. Their flight muscles didn’t work properly.

“I felt like nature pointed me in this direction and I had to follow this lead,” Saba said.

In a May 14 paper published in Public Library of Science ONE she described the results of following that lead. She discovered how the protein, called S1P, triggers muscle stem cells called satellite cells to repair muscle damage. Saba, who is senior scientist at Children’s Hospital Oakland Research Institute (CHORI), was working with a CIRM training grant recipient Kenneth Loh. Loh is first author on the paper.

Saba’s father, the muscle biochemist, is reportedly thrilled that his daughter is taking on the family business.

A press release describes how this serendipitous work could help people with forms of muscular dystrophy:

“These findings are important especially for certain muscle diseases or “myopathies” that can affect children,” states Dr. Saba. The most common and one of the most severe myopathies is Duchenne Muscular Dystrophy, a disease that affects young boys and often leads to death from respiratory and heart failure in a patient’s twenties. Although patients with Duchenne Muscular Dystrophy start out life with enough satellite cells to repair the patients’ degenerating muscles, over time the satellite cells fail to keep up with the rate of muscle degeneration. “We found that mdx mice, which have a disease similar to Duchenne Muscular Dystrophy, are deficient in S1P. We were able to increase the S1P levels in the mice using a drug that blocks S1P breakdown. This treatment increased the number of satellite cells in the muscles and improved the efficiency of muscle regeneration after injury.”

I really like this study in part because it is a great example of the twists and turns of research. Saba says half of her cancer lab is now dedicated to muscle research.

On our website we have a list of CIRM awards focusing on muscular dystrophy. These range from very basic awards, with researchers trying to better understand the disease, to awards in which researchers are trying to turn discoveries into new therapies for this devastating disease.

A.A.

Stem cells used to treat muscular dystrophy in mice

Muscular dystrophy is a particularly tragic—and lethal—disease that currently has no effective therapy. But researchers at the University of Minnesota have made some progress in using stem cells to treat a form of muscular dystrophy in mice.

Muscular dystrophy can occur in adults but is most common in children and causes the person’s muscles to atrophy. When the muscles break down, the stem cells within the muscle aren’t able to replace the lost tissue. It’s a devastating condition

Stem cell researchers have, in the past, thought that one approach to treating the disease could involve maturing embryonic stem cells or reprogrammed iPS cells into muscle-specific stem cells (called satellite cells) and transplanting those into the muscles of people with the disease. The problem has been that, until now, nobody had been able to prod those embryonic or iPS cells to form the sought-after satellite cells.

The group from Minnesota finally worked out the right combination of signals that would push the cells to form the muscle precursors in a lab dish

Using their technique, the group generated large numbers of satellite cells from either human embryonic stem cells or iPS cells. When they transplanted those cells into mice with a form of muscular dystrophy those mice regained some strength. A story in Medical News Today quotes the lead researcher Rita Perlingeiro:

“Seeing long-term maintenance of these cells without major adverse side effects is exciting. Our research proves that these differentiated stem cells have real staying power in the fight against muscular dystrophy.”

In the paper, published May 4 in Cell Stem Cell, the group wrote that they think they can make enough of the appropriate type of cell to be able to treat a person with muscular dystrophy. However, they do have several obstacles to overcome. The way they generated the muscle stem cells would not be a safe approach for use in humans. Despite that hurdle, the scientific director of clinical research at the University’s Stem Cell Institute and renowned blood and marrow transplant expert John Wagner said the work has promise:

“This research is a phenomenal breakthrough. Dr. Perlingeiro and her collaborators have overcome one of the most significant obstacles to moving stem cell therapies into the treatment of children with devastating and life threatening muscular dystrophies.”

CIRM also funds researchers investigating stem cell therapies for muscular dystrophy. A complete list of those awards with descriptions of the research is available on our website.

A.A.