Guest blogger Alan Trounson — March 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.

The lead article in this month’s report focuses on CIRM-funded work in Irv Weissmann’s lab at Stanford. It reports on a protein on the surface of cancer cells that in essence says “don’t eat me” to the immune system cells that are supposed to seek out, engulf and destroy tumor cells. This cell surface protein is called CD47. More important, an antibody that blocks CD47 seems pretty effective in reactivating the immune system’s attack on the tumors—at least in mice. My colleague Amy Adams blogged about this research here.

There are two quite different aspects of this research that excite me. First, it is a finding that could be very important clinically that clearly derived from basic research. Irv’s team originally found the cell surface protein when they were trying to understand the fundamental relationship between the immune system and cancer cells. It turns out CD47 is expressed on the leukemia cells they were studying, but highly expressed on leukemia stem cells, which are hypothesized to be responsible for the tendency of leukemia to relapse after treatment.

The other reason to be excited about this work is that it goes counter to much of the direction of cancer research today. Many of the exciting new therapies are coming from an increased understanding of how individual most cancers are from one another. The newest therapies tend to be most effective for a narrow set of tumors, often with specific genetic compositions. This latest work showed the single antibody to be able to shrink and sometimes eliminate many different solid tumors. The Stanford team reported results for cancer cells from seven different human tumors transplanted into mice. Such a broad-spectrum cancer treatment, even if it has to be paired with other agents, has the potential to be less costly because of the market size.

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


David Serrano Sewell reflects on MS Awareness Month, the need for therapies

David Serrano Sewell is a patient advocate member of CIRM’s governing board. His bio is available on our website.

When I began serving on the CIRM governing board in 2005 it was with the hope that I could be part of guiding the agency’s decisions in a way that would benefit the many people in California who are looking to CIRM for new therapies.

I have been active with the Northern California Chapter of the National Multiple Sclerosis Society since my own diagnosis with MS. Right now, there are no cures for the disease, just drugs that can help slow it’s progression or mitigate the symptoms, though those also come at a price. The most common drug causes flu-like symptoms and the effectiveness diminishes over time. It’s a disease in need of more effective therapies.

March is National Multiple Sclerosis Awareness Month, and it seems like a good time to look back on what we’ve accomplished at CIRM to find a stem cell-based therapy for the disease.

We’ve funded two awards to researchers who are directly studying MS. One is to Thomas Lane at the University of California, Irvine (here is a summary of that award). He is looking at ways of using human embryonic stem cells to replace the insulation surrounding nerves that is lost in MS. The other is to Samuel Pleasure at the University of California, San Francisco (here is a summary of that award). He is attempting to start with nerve stem cells and mature them into precursors of the types of cells that form that insulation. He then proposes transplanting those precursors into people with MS to treat the disease.

Both of these projects are in their early stages and it’s too soon to know whether they will blossom into new therapies. What I do know is that without these kinds of early stage projects we will never see more effective therapies for MS reaching patients.

As part of the governing board I am part of the group that makes decisions not only on which individual awards to fund, but also on big picture issues. We make decisions on whether new stem cell research facilities would speed new therapies, and how to ensure that California remains a leader in stem cell research by funding training and career development. Although those awards don’t have a single-minded focus on MS, they will help bring new therapies for all the patients who I was elected to represent.

I hope in future MS Awareness Months to be able to point to new research projects picking up where these early stage ones leave off. Getting from early research to promising therapies is a long and often difficult process, but it’s one that I’m proud to play a role in directing.

You can read more about MS on the CIRM website.

David Serrano Sewell

Single antibody developed by CIRM grantee fights many tumors

Stanford researcher Irv Weissman made the news yesterday when he published a paper showing that  a single antibody-based therapy can effectively slow the growth and in some cases eliminate many different kinds of human tumors, at least in mice.

Weissman leads a $20 million CIRM disease team that is developing an antibody-based therapy to treat leukemia. In previous work, Weissman had found that leukemia cells evade the immune system by placing a protein on their surface that tells the immune system “don’t eat me.” Blood-forming stem cells in the bone marrow also use that protein on occasion to avoid immune detection, as do red blood cells.

Weissman and his group are developing an antibody that latches onto that protein, called CD47, and makes the protein invisible to the immune system, particularly immune cells called macrophages. Without their “don’t eat me” signal, the macrophages ingest the leukemia cells.

Now, it looks as if that antibody therapy might be effective for cancers in addition to leukemia. Weissman and his group published a paper March 26 in the Proceedings of the National Academy of Sciences showing that CD47 is present at high levels on the surface of tumor samples taken from people with ovarian, breast, colon, bladder, brain, liver and prostate cancers.

What’s more, their antibody therapy prevented the growth of those tumor cells that had been implanted in mice, and in some instances eradicated them. A story in the Los Angeles Times describes the work:

Placing the cells in lab dishes, the team administered an antibody: a protein that binds to CD47 and blocks it from warding off immune system cells. Macrophages ate the cells.

The researchers then implanted human tumor cells in mice for further study. They allowed the cancers to grow, and administered the antibody against CD47.

Antibody treatment inhibited the growth of almost all of the solid tumors and was able to wipe out some smaller cancers altogether, according to the report, which was published Monday in the journal Proceedings of the National Academy of Sciences.

A press release from Stanford quotes Weissman:

“Blocking this ‘don’t-eat-me’ signal inhibits the growth in mice of nearly every human cancer we tested, with minimal toxicity. This shows conclusively that this protein, CD47, is a legitimate and promising target for human cancer therapy.”

A story in Science quotes Weissman talking about testing the drug in human trials:

Weissman’s team has received a $20 million grant from the California Institute for Regenerative Medicine to move the findings from mouse studies to human safety tests. “We have enough data already,” says Weissman, “that I can say I’m confident that this will move to phase I human trials.”


Stem cell therapy for heart attack

We are rolling out our 2011 Annual Report stories throughout March. The full report will be posted online and available for download later this month.

Each year in our Annual Report we highlight some of the patients and scientists who came to speak to our governing board about the search for cures. This year one of our stories focuses on research by Eduardo Marbán, who is leading a CIRM disease team developing a therapy to help repair damage after a heart attack.

Marbán spoke to our governing board about a clinical trial using the patient’s own heart cells to repair the damaged heart. This trial is the precursor to the next generation research being funded by CIRM, which uses heart cells from a donor heart. (We blogged about his Dec. 8 talk here.)

Marbán brought with him Frank Lesikar, who had participated in Marban’s clinical trial after a heart attack had damaged his heart. From the annual report story:

I’m in better shape than I’ve been in in years,” he says. Some months after his attack, he enrolled in a clinical trial, in which researchers harvested a bit of tissue from his heart, coaxed stem cells from the tissue to grow, and put the cells back into his heart again. The results? Lesikar’s heart is functioning better and the scar left from his heart attack appears to be reduced.

The study that helped Lesikar is one that led up to a $5 million disease team award from CIRM to fund the next generation therapy.

Read more about Lesikar’s story and about Marbán’s research in the annual report story posted online. This is the seventh annual report story we’ve posted. Here are the others:

The full report will be available for download later this month.


Progress report from the CIRM disease teams

At last week’s meeting in Sacramento, our governing board heard an update on the progress being made by the 14 CIRM disease teams that they had approved in October 2009. A list of those teams is available on our website.

Funding teams of researchers with scientific and regulatory expertise to work together was an innovative step—one that CIRM anticipates will help those groups get their therapies to clinical trials faster than they would without this team approach.

Before issuing the awards, CIRM’s science staff worked with the teams to come up with milestones and success criteria. Periodically, CIRM meets with the teams along with a group of experts who have experience taking therapies into clinical trials and through to approved therapies.

Taking the advice of these experts into consideration, CIRM decides whether the projects are achieving the agreed upon milestones. These assessments help protect the state’s financial investment by making sure the teams are focused and have the resources and expertise they need to achieve the goals of their research. It also identifies projects that need additional support, or ones in which the original idea is not ready to continue.

Ellen Feigal, CIRM’s senior VP of R&D, summarized the progress being made by each of the teams. You can read the background material she gave to the board members, which has detailed information about the achievements by each group.

The first CIRM and expert assessments of the disease teams met in 2011, at the 12 to 18-month milestones. The group found that thirteen of the projects are on a trajectory toward meeting their milestones. Of those, one is undergoing some revisions to focus the work. One of the projects is not continuing. CIRM will save roughly $13 million on this award through early termination.

The team that is not continuing, led by researchers at the University of California, San Francisco, produced data that did not meet the agreed upon success criteria. That criteria had to do with selecting the best stem cell type to use in their proposed therapy for a type of brain tumor called recurrent glioma.

During the course of their work, the team had generated some new methods that may be useful for other researchers and published two papers. These lessons learned are part of the iterative process of trying to create new therapies.

As with all potential therapies, none of the therapies developed by the CIRM-funded teams can enter clinical trials until they provide evidence to the U.S. Food and Drug Administration (FDA) that the therapy is safe to test in humans. Carrying out these experiments is costly and brings with it the possibility that the original idea won’t work. The researchers then needs to go back a step and take what they learned from the first attempt and use those lessons to guide other approaches.

CIRM created the disease teams as a way of funding this critical stage of research. We instituted the milestones and the input of product development experts to better position the teams for success and protect the state’s financial investment. This way, we are trying to ensure the teams have the resources and expertise they need to bring these much needed therapies into clinical trials in humans.

CIRM and our panel of experts will be meeting with the thirteen teams at their 24- to 30-month milestones in 2012 to assess progress. Regardless of the outcome of those assessments, each of the teams is producing data and gaining experiences that will help guide the next generation of stem cell-based therapies.


California’s diverse high school students get additional stem cell lab experience

Yesterday’s governing board meeting in Sacramento included an agenda packed with meaty discussion items. We’ll be blogging about those items over the next few days. You can read the agenda here to see what was up for vote and discussion. We always audiocast our board meetings and put that information in the agenda for those who want to hear the conversation in real time. Transcripts are also posted a few weeks later to the page listing all public meetings.

We encourage people to attend our board meetings in person. For those who can’t make it, here’s one scientist’s impression of what a meeting is like. Paul Knoepfler is a CIRM grantee at the University of California, Davis, who also has a blog about stem cell science. He attended yesterday’s meeting and introduced himself to the board as both a scientist and a patient advocate—he is a cancer survivor.

One notable item from yesterday was the decision by our governing board to support $1.7 million for a high school summer internship program called the Creativity Awards. We’ve blogged quite a bit about this program including this post previewing their meeting, this post about the work the students presented at their meeting, this post about one of the recipients who went on to be a semifinalist in two national science competitions, and this post about an award going to one of the Creativity Award hosts.

The reason for all these posts is that we’re really excited about this program. It brings in high school students from all socioeconomic backgrounds and gives them experience in California’s stem cell labs.

Here’s what CIRM president Alan Trounson had to say about the awards in the press release from yesterday’s meeting:

“This program exposes high school students to cutting edge medical research and encourages the kind of creative thinking that leads to groundbreaking discoveries,” said Alan Trounson, CIRM President. “The pilot program last summer demonstrated the demand for stem cell research opportunities among California’s young people. Expanding the program and extending it for three years will inspire more students from all socioeconomic backgrounds to pursue careers in stem cell science and nurtures the creative thinking that will help them be successful.”

That release also lists the nine recipients of the awards. This video gives a flavor of the kinds of research carried out by the diverse students who participated in last year’s pilot program of the Creativity Awards:


Stories of Hope: finding a therapy for neuromyelitis optica

We are rolling out our 2011 Annual Report stories throughout March. The full report will be posted online and available for download later this month.

Each year in our Annual Report we highlight some of the patients and scientists who came to speak to our governing board about the search for cures. This year one of our stories focuses on a rare disease called neuromyelitis optica, also known as NMO or Devic’s disease. You can read that story here.

Neuromyelitis optica is so rare that when Ali Guthy was diagnosed her mother Victoria Jackson could only find one expert in the U.S. to treat her daughter. Jackson, who was the creator of Victoria Jackson Cosmetics, quickly started the Guthy-Jackson Charitable Foundation and began funding researchers to work together to better understand and hopefully find a therapy for the disease. CIRM chose to highlight Jackson and NMO because it provides such a vivid example of what dedicated patient advocacy can accomplish.

Last year CIRM produced a video about Jackson’s efforts to start the foundation and turn her life’s focus, as she says, from “mascara to medicine.”

Like multiple sclerosis, NMO is a disease in which the body’s immune system attacks the insulation that surrounds nerves. Michael Yeaman, who studies the disease at UCLA, told the governing board that until recently the only way of slowing the disease was through sterioids, which he said leaves patients vulnerable to other infections and can increase the risk of cancer. He said:

“Ultimately, reversing the damage caused by NMO or other autoimmune diseases will require regenerative medicines, and stem cells will play a key role in that respect. To restore the central nervous system, we’re going to need regenerative help.”

Read more about Jackson’s story and about progress toward therapies in the annual report story posted online. This is the fifth annual report story we’ve posted. Here are the others:

The full report will be available for download later this month.


Stem cell image of the week: Pancreatic cells for a diabetes therapy

Pancreatic cells derived from human embryonic stem cells. ViaCyte, Inc.

This colorful river of cells is really a side shot of pancreatic cells within a thin device. The cells, which were matured from embryonic stem cells, are being developed as a therapy for diabetes by a CIRM-funded disease team led by ViaCyte in La Jolla.

The group is maturing embryonic stem cells into the type of pancreatic cells that produce insulin in response to blood sugar. These are the cells that are destroyed in people with diabetes. The group puts those cells within a thin device to protect them from the body’s immune system. When they implant the device in animals, the cells appear to function properly and release appropriate amounts of insulin to control blood sugar.

The group is now working toward clinical trials to test the device in humans. We wrote more about the ViaCyte-led team last week. You can read that story and watch a video about the work here.

We have more diabetes images on our Flickr site, where you can also learn more about what the different colors represent in today’s image.


Stem Cell Therapy for the Economy

We are rolling out our 2011 Annual Report stories throughout March. The full report will be posted online and available for download later this month. Today we are introducing a story about the economic benefits of funding stem cell research in the state: Stem Cell Therapy for the Economy.

CIRM’s primary mission is to develop new stem cell-based therapies for disease. But the process of driving those new therapies has other benefits to the state—economic ones.

Scientists and industry have moved to California due in part to hopes of receiving funding from CIRM, and also to support the growing stem cell research industry. With these companies and new labs come jobs, tax revenue and additional non-CIRM grant money.

A few years ago CIRM commissioned a report to find out how many jobs and associated tax revenues CIRM had created for the state. As we say in our annual report story:

Counting only the first $1.1 billion in funding, by 2014 CIRM’s initiatives are expected to have brought in $200 million in tax revenue to the state and created 25,000 job years—that’s economist speak for employing 25,000 people for a year, or 5,000 people for five years. Those jobs each have ripple effects for the state when employed people pay taxes and buy groceries, electronics and homes.

Our story specifically describes research by Robert Wechsler-Reya and Peter Coffey, who set up labs in California to study childhood brain tumors and blindness, respectively.

Wechsler-Reya, who is now director of the Tumor Development program at the Sanford-Burnham Medical Research Institute in La Jolla, moved into the new Sanford Consortium building partially funded by CIRM (read more about the CIRM-funded facilities here). In our story he said that facility and the collaborations it encourages was one reason to move to California from Duke University:

“One of the amazing things about this place is that there are a lot of interactions not only among academic institutions, but also between academia and industry. It is the kind of thing that I could not have done back east.”

Read our story online for more about Wechsler-Reya, Coffey, and The Jackson Laboratory West, which greatly scaled up after receiving a CIRM award in 2009. The most important aspect of these grantees’ work is their progress toward therapies. But it’s good to know that the state’s growing stem cell industry is good for the economy as well as eventually being good for patients.

This is the fifth annual report story we’ve posted. Here are the others:

The full report will be available for download later this month.


CIRM Bridges students at Parkinson’s Institute get job training, experience

The Parkinson’s Institute in Sunnyvale not only carries out CIRM-funded research into therapies for Parkinson’s disease (you can see a list of their awards here), but they are also training the next generation of researchers to continue that work in the future. They’ve partnered with the San Jose State University CIRM-funded Bridges program to provide stem cell research experience to undergraduate and masters students. The Parkinson’s Institute recently featured their two Bridges interns Orlando Macaranas and Leo Rodriguez in their newsletter, writing:

“Though eventually Parkinson’s will be a disease of the past, research will continue, and we are proud to help foster the next generation of researchers.”

One goal of the Bridges program is to provide students with the kinds of hands-on experience they need to work in California’s growing stem cell industry. The newsletter quotes Macaranas:

“Being able to work in a lab and gain hands-on experience has been invaluable. I am more prepared for a job after graduation than my peers who have not completed this program.”

Orlando Macaranas, CIRM Bridges student

Rodriguez said:

“The Parkinson’s Institute is a perfect place to gain lots of experience. The stem cell researchers here are eager to teach and I have been given more responsibility and increased my skills more than I would have at a much larger facility.”

Leo Rodriguez, CIRM Bridges student

This page on our website describes the Bridges program here you can see the locations of Bridges programs and their mentor institutions [pdf]. You can also see a list of the Bridges award recipients in our list of all funded CIRM awards.

Here is a video shot at last year’s Bridges meeting where the students discussed their research progress.