Forty years ago today President Nixon signed the National Cancer Act, allocating $1.5 billion over three years for cancer research.

The Dana-Farber Cancer Institute has written an excellent piece on their blog about where the field has come since 1971. They write:

Forty years later, the War on Cancer can claim countless successes against one of the most resilient and recalcitrant enemies mankind has faced.

Some cancers that were once almost invariably fatal, such as pediatric leukemia, are now cured in the vast majority of cases. In kidney cancer, the five-year survival rate – the percentage of patients alive five years after diagnosis – has increased from about 50 percent in 1971 to more than 70 percent today. In colon cancer, the rate has increased from 52 to more than 66 percent over the same time period. Death rates for cancers of the breast, liver, lung, prostate, and several other organs and tissues have been declining for the past 10-20 years.

…

Despite all the strides over the past 40 years, cancer remains one of the biggest health challenges we face. The good news is that advances in the understanding of cancer at the basic, molecular level have positioned us to make even greater progress in the years ahead.

CIRM is playing an active role in the ongoing search for better cancer therapies. Of our disease-focused awards, cancer makes up 22% of our funding (you can see charts of our funding allocations here).

CIRM has eight awards working towards new therapies for cancers including leukemias and solid tumors such as those that form in the colon, brain and ovaries. Of those, four projects (two in leukemia and two in brain tumors) are part of our disease team programs, which all have the goal of submitting an application to the Food and Drug Administration by 2014 to begin a clinical trial. You can see a list of all our therapy development projects with links to those project descriptions in our online portfolio.

Although we can’t know in advance which of these projects will be successful, CIRM is proud to be part of the ongoing search for new cancer therapies.

A.A.

Todd Dubnicoff is CIRM’s videographer and video editor

At many CIRM governing board meeting, we set time aside to hear from researchers, clinicians, and patients about the hope of stem cell research in a particular disease area. We film each of these Spotlight on Disease seminars so that the scientists’ progress and the patients’ stories are available to the public (a video archive of past Spotlights is here). At the December 8th Spotlight, the board heard about the hope for a stem cell based heart failure treatment that is showing promising results here and now in a clinical trial for patients (watch that video here).

“An easy painless miracle.” That’s the way Fred Lesikar, one of the Spotlight speakers and a clinical trial participant, described the procedure that used his own heart stem cells to regenerate his scarred heart tissue injured by a massive attack two years ago at the age of 59.

The procedure is straight-forward: clinicians obtain a small tissue sample from the patient’s heart during a 15 minute procedure under local anesthetic. Under specific laboratory conditions, stem cells spontaneously grow out of this tissue sample. These cells are then harvested and delivered back into the patient’s coronary artery. Lesikar told the board that he is thrilled with the results:

I was in pretty bad shape…Next week it will be two years since I had the stem cells put in…it wasn’t like a light switch going off but by the time I got to a year I was feeling great…Now I’m flying down to Costa Rica tomorrow, the day after tomorrow I’ll be tromping through the jungle and my only concern is that the people with me aren’t going to be able to keep up.

Eduardo Marban, MD, PhD, director of the Cedars-Sinai Heart Institute, led this first-in-human clinical trial and was the main speaker at this month’s Spotlight. Marban summarized the hallmarks of heart failure after a heart attack and described the results of the trial:

One quarter of heart attack patients end up with so much scar that life expectancy is compromised…Once the scar occurs it’s irreversible…At one year, the subjects receiving the stem cell therapy have 12 to 13 grams less scar than they did at the beginning of the study. That in of itself is a good thing but what really got us excited was the fact that when we looked at the living heart muscle, those subjects have 22 grams of new living heart muscle…That’s equivalent to restoring about half or more than half of the lost heart muscle in these subjects (compared to no change in control subjects).

Marban also showed results of pre-clinical studies funded by a CIRM Disease Team grant, which uses an alternate preparation and delivery method of the heart stem cells. These studies will form the basis of an FDA application in the second quarter of 2012 to perform a follow-on clinical trial.

T.D.

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In October the European Court of Justice issued a ruling that inventions created from human embryonic stem cells are not patentable. We wrote a few blogs at the time giving voice to different perspectives on what that ruling might mean. (Those blogs are here and here.)

This month, CIRM President Alan Trounson weighed in on the possible repercussions of the decision in the journal Cell Stem Cell (The abstract is available here, full access requires a subscription). Trounson’s letter is one of several opinions on the case that appear in this issue. Writing with Nancy Koch, CIRM legal Counsel, and Elona Baum, General Counsel and VP of business development, Trounson said:

Our view is that the impact of the recent Court ruling on stem cell research and regenerative medicine will be significant but varied. In some instances, the ruling may deter European hESC research, in others such research may nonetheless continue or even increase; in still others, no impact may occur.

The group wrote that they don’t expect the ruling to have a significant impact on basic research involving human embryonic stem cells. However, they suggest that the situation is more complicated for the type of research that translates basic human embryonic stem cell research discoveries into therapies. They write:

At this stage of research and development, profit-driven biotechnology and pharmaceutical companies are more actively involved. To the extent that the lack of patent protection following the Court ruling decreases the profit available (e.g., because patented inventions cannot be licensed and injunctions cannot be obtained to protect hESC patented inventions), biotechnology and pharmaceutical companies may be less motivated to invest in European hESC research. That effect may be even more dramatic for startup companies. A strong patent portfolio traditionally has been a prerequisite for attracting venture capital in the life sciences field.

However, they don’t predict a dearth of European commercial investment in embryonic stem cell research and technology. That’s because even though companies can’t patent discoveries, they may still be able to protect their work as traditional trade secrets. Moreover, the European regulatory authorities may require data from trials conducted in the EU before approving certain future stem cell-derived products

They also suggest that the ruling could lead to relocations both from the EU to the U.S. and the reverse. European companies whose business model relied on embryonic stem cell patents might relocate to the U.S. where those patents still hold. Companies in the U.S. who are slowed by patents held by others might relocate to the EU where those patents aren’t enforceable.

How these different factors play out remains to be seen, but the group does end on a hopeful note. They conclude by saying that they expect at least some of the critical human embryonic stem cell research taking place in the EU to flourish.

A.A.

The board meeting last week was a day for following up on recommendations. In additional to the Opportunity Funds, which we blogged about earlier in the week, the board also approved a proposal for creating a stem cell bank. Stay with me here. This may not sound as exciting as funding new science or creating worldwide partnerships, but it’s important. Here’s why.

Imagine for a second that you decide you want to read those last few Jane Austens that you didn’t read in college. You go to the library, check them out, and enjoy. Right? But imagine that instead of going to a library you had to call around the neighborhood to track down the books, then drive to four different homes and sign four different book loan agreements and after all that some of the books have torn pages. It might seem like a better idea to just reread one of those old Agatha Christies on the shelf.

That’s where stem cell research is today. Say a researcher wants to compare stem cell lines from people with autism to find drugs that alleviate signs of the disease in a dish. That researcher would have to call around to several institutions, navigate a variety of materials transfer agreements and, basically, spend a lot of time on the phone rather than doing research. In yesterday’s blog, my colleague Geoff Lomax quoted Steve Peckman from the UCLA Broad Stem Cell Research Center talking about how these agreements –called MTAs—can hinder access to stem cell lines.

One way for CIRM to accelerate research is by creating more of a library system for stem cells – except we don’t want the cells back. This kind of bank is what was recommended at a banking workshop we held back in November 2010. (You can read a report from that workshop here.)

At last week’s meeting, Uta Grieshammer from our science office described CIRM’s $30 million proposal for creating such a bank. It will consist of three parts. First up will be awards to investigators who will go out and collect tissue samples from individuals with genetic diseases. The goal is to get samples from 1200 people.

Next, CIRM will give a single award to an organization that will take those samples and reprogram them into embryonic-like cells, called iPS cells. These cells have the ability to form every tissue in the body, and still retain the genetic make up of the person who donated the sample. These cells can then be matured into the cell type that goes awry in the disease as a way of studying that disease in a dish. In the past few years this technique has been used to create models of ALS, schizophrenia, Parkinson’s disease and autism, among others.

Finally, CIRM will fund a group to bank all these newly created cells, along with other stem cell lines. With this resource, that same researcher hoping to study autism cell lines could go to one place, navigate one materials transfer agreement and receive cells that are consistently quality controlled. The cells will be available to people in California and worldwide.

A.A.

Geoff Lomax is CIRM’s Senior Officer to the Standards Working Group 

Is the ability to obtain embryonic stem cell lines hindering research, what factors influence access, and does availability vary by state? These questions have been the subject research and their answers are not entirely clear. A recent publication in Nature by Aaron Levine of the Georgia Institute of Technology suggests that access issues do impact research. In his paper, he writes:

“an inability to acquire certain hESC lines have likely hindered hESC science in the United States.”

This conclusion is based on a survey of stem cell scientists in the United States. Levine focused his discussion on the subset who reported using human embryonic stem cells. A sizable number of these scientists–38%–reported excessive delay in obtaining lines and 28% reported they were unable to acquire a stem cell line they wanted to study. Factors attributed to delays included problems with materials transfer agreements (MTAs) and an inability to obtain approval from an institutional oversight committee. Based on these findings, Levine writes:

“These results suggest scientists in the United States cannot conduct comparative studies with a diverse set of hESC lines and suggest that access issues have contributed to this situation.”

I found these results intriguing because in a recent study quantifying the use of hESC lines by CIRM researchers, my colleagues and I found that scientists had obtained a diverse array of embryonic cell lines – 138 unique lines including 17 newly derived hESC lines. I suspected the apparent discrepancy in findings may be related to the research environment in California and other states with policies designed to support access to and creation of human embryonic stem cell lines. The answer to the question of whether availability varies by state is not clear because Levine’s responses are not geography correlated.

Our findings suggest widespread access in California, but it is important to keep in mind we examined what lines researchers ultimately accessed, not what they were unable to obtain. To gain further insight, I did a quick survey of my Science Office colleagues. Many hadn’t heard of cases where access to cell lines had been a deterrent to research for our grantees. I also queried grantees who were carrying out comparative studies. Jeanne Loring of the Scripps Research Institute has a CIRM grant to compare cell lines. When I emailed her she said:

“We’ve had no trouble getting hESC lines from collaborators all over the world. There are hundreds of cell lines available, and most are of good quality.”

Another colleague did recall instances where there were delays in obtaining cell lines, so I emailed Steve Peckman, who is Associate Director of the UCLA Broad Stem Cell Research Center. He did offer specific examples where material transfer agreements were a source of delay. In addition, Peckman indicated the NIH restrictions on the use of certain popular lines, such as HUES 9, did impact approval by institutional oversight committees even in cases where no NIH funding was involved, so perhaps California researchers were not immune to access issues.

Peckman also said that a game changer at UCLA was the ability to study newly derived UCLA 1-6 hESC lines created with CIRM funding (here is a list of all cell lines considered “acceptably derived” by CIRM). He suggested new cell line derivation has been a tremendous benefit for researchers, potentially attenuating problems encountered elsewhere. He noted, however, that UCLA and others are not well equipped to distribute lines outside their home institution, which could explain Levine’s findings that certain individual researchers were having a hard time accessing lines. Peckman’s solution was to support the development of a banking and distribution network with uniform material transfer agreements.

Peckman’s observations are reassuring in light of the decision by CIRM’s board to move forward with CIRM’s Human Pluripotent Stem Cell Initiative. The initiative includes a “Bank Award”. The concept proposal for this award says:

“California researchers have already generated many disease‐specific human induced pluripotent stem cell (hiPSC) and human embryonic stem cell (hESC) lines, many with CIRM funds… CIRM intends to provide funds for the establishment of an hPSC repository located in California that will bank and distribute high quality, disease specific hiPSC and hESC lines generated in California for research use.”

The comparative ease of access in California, as evidenced by Loring’s work, may be attributed to our comprehensive scientific, regulatory and facilities programs designed to facilitate research. CIRM’s programmatic efforts are consistent with Levine’s suggestion that “funding agencies … encourage research using multiple diverse hESC lines.”

We are always interested in hearing more. If you have experience accessing and utilizing hESC lines, we encourage you to comment below or contact me glomax@cirm.ca.gov.

G.L.

Today a CIRM-funded disease team working toward a therapy for type 1 diabetes received additional support and endorsement from the Juvenile Diabetes Research Foundation (JDRF). The project, led by San Diego-based Viacyte, received almost $20 million in funding from CIRM in October 2009.

The goal of the ViaCyte project is to mature embryonic stem cells into a type of cell that normally produces insulin in the pancreas. These are the cells that are destroyed in people with diabetes. The group plans to put those cells in a device that protects them from the immune system, then implant that device in the body where it is hoped that the cells will mature to produce insulin in response to blood sugar. The cells are effective in animal models, the company says.

According to a press release from JDRF:

The three-year series of preclinical studies being co-funded by JDRF will help ViaCyte prepare the information necessary to apply for regulatory approvals to study the system for safety and efficacy in people with T1D.

The release goes on to quote leaders from JDRF, ViaCyte and CIRM:

“Encapsulation research is one of JDRF’s priorities because of the profound possibilities it holds for many avenues of research for type 1 diabetes,” said Julia Greenstein, JDRF’s assistant vice president for Cure therapies. “We’re excited about partnering with ViaCyte to explore the use of encapsulated stem cell-based replacement. This type of innovative therapy could revolutionize the way people live with type 1 diabetes, and may also reduce the risk of dangerous complications that often result from extreme high and low blood sugars.”

“We are thrilled to be partnering with JDRF, the leader in the field of support for diabetes research,” said Allan Robins, Ph.D., acting CEO from ViaCyte. “ViaCyte’s goal is to create a product that will free people with diabetes from insulin dependence for the long-term, and we believe this therapy has the potential to transform lives.”

“At CIRM, we have long had the goal of leveraging the financial and intellectual capital of California with other funds and talent from around the state and around the world, and the decision by JDRF is a clear example of how these partnerships can enhance the opportunities to get to the end goal of a therapy for patients,” said Alan Trounson, president of CIRM. “We are proud to have JDRF as a partner in working with ViaCyte and their scientific team to bring a potentially life-changing therapy for people with diabetes to the clinic.

Here’s more information about the ViaCyte disease team project and more about CIRM funding of diabetes research.

This video features ViaCyte’s Eugene Brandon discussing the company’s approach:

A.A.

On December 8 of last year, CIRM received the insights and recommendations from a blue ribbon panel of external experts charged with evaluating the agency’s progress to date. (Here is a copy of that report, and CIRM’s press release.)

Less than a year later, on October 26, 2011 the ICOC approved the first of a three-part Opportunity Fund to address those recommendations. (A press release from October board meeting is available here.) And, just days ago on December 8th, a year to date from the expert’s report, the governing board approved the final two proposals. (That press release is available here.)

With all three programs of the Opportunity Fund approved, CIRM will be able to address the major recommendations of that panel: namely to create an agile and proactive grant program with flexible processes that synch up with industry, all geared at capturing great science and maintaining the progress of our strong research programs.

When CIRM first received the review panel’s report, the question was how could the agency address the recommendations within its legal and operational frameworks. All new science funded by CIRM has to go through a review by outside experts, which takes time, and state funds have to stay within California. To address these questions, CIRM held a brainstorming session to think about the most effective ways of meeting the recommendations.

What the CIRM science and legal offices came up with were three initiatives. The first of these, called the Strategic Partnership Funding Program, was approved at the October board meeting. This $30 million initiative responds to the review panel’s recommendation that CIRM attract industry partnerships through a funding approach that is more aligned with industry needs.

According to Elona Baum, CIRM General Counsel and Vice President of Business Development, who led the development of that program, the Strategic Partnership Funding Program will help our grantees team up with industry partners who can help them overcome regulatory issues and design effective clinical trials. These partners will also be needed to fund Phase III clinical trials.

The two pieces of the Opportunity Fund approved on December 8th are the $12 million Bridging fund, spearheaded by Patricia Olson, Executive Director of Scientific Activities, and the $15 million External Innovation Initiative, led by Ellen Feigal, Senior VP of Research and Development.

The External Innovation Initiative was developed as a way of leveraging California expertise to further great science taking place outside of California. CIRM has formed funding relationships with 12 countries, two international states, one domestic state, two foundations, and most recently CIRM’s collaborative relationship with the National Institutes of Health. (More information about those relationships is available here.) If great science is taking place in one of those jurisdictions, CIRM can facilitate a collaboration with a California scientist whose expertise will speed the science. CIRM only funds the portion of the research within California – protecting the state’s investment – but that funding can speed research toward disease therapies taking place around the world. Even if a therapy isn’t developed in California, Californians benefit from the results.

The Bridging Fund will play a critical role in keeping promising research moving forward. Imagine, you are a CIRM grantee with an Early Translational Award that produced promising results. But your funding ends, and you won’t know if you got your next CIRM award for several months. What do you do? You stop the research until you get more funding either from CIRM or from some other source. This stop and go nature of funding slows promising projects. The Bridging Fund will provide stopgap funding for those researchers who are waiting on the next big grant, keeping the research moving toward patients.

As Olson said, “I think these programs go a long way toward addressing the key concerns of the external advisory committee. Next comes implementation.”

The announcements describing each of these programs will be posted to the CIRM website in the first half of 2012.

A.A.

Jonathan Thomas is Chair of the CIRM governing board

Yesterday our governing board met for the first time since Geron announced the decision to terminate their stem cell research program. I wanted to take that opportunity to address the board and let them know my strong commitment to CIRM’s stem cell research program.

When Geron made their announcement our immediate concern was for the patients and their families who were disappointed at the termination of a trial that was a source of such hope for the future. Geron has been a true leader in the field and a source of inspiration for patients and their families. They broke new ground, becoming the first to start a Food and Drug Administration-reviewed trial based on human embryonic stem cells. Their efforts laid the groundwork for the two additional trials now underway for forms of blindness and for those trials that are close to submitting applications to the FDA.

However, Geron is a business. The company decided that their cancer therapies were farther along than the stem cell trial and when they held the stem cell program against the prism of economic reality they made a business decision to end the trial. The company is now looking for a partner to carry the research forward.

There are those who have extrapolated Geron’s business decision to question stem cell science. I say to those people: If you were to query the many researchers worldwide and companies involved in developing products you would hear unwavering enthusiasm for pursuing stem cell technology.

I was just at the excellent Stem Cells on the Mesa meeting in La Jolla where I heard from those researchers and investors. We spent the first day hearing about the incredible scientific advances taking place in the stem cell field. The next day we attended a business and investor partnering forum (sponsored in part by CIRM) where the same message of enthusiasm for stem cell science echoed just as strongly.

CIRM’s award to Geron was just one of the 44 projects in 26 disease areas that are in various stages of working toward clinical trials. (I blogged about those projects recently.) We remain optimistic about those research programs and are totally committed to the projects we have funded to-date and to the research we will fund in the future.

J.T.

Elongated green cells are sensory neurons – which sense smells and relay that information to the brain – that originated from olfactory stem cells in the nose. Cells labeled in red are immature cells in the process of differentiating into neurons and other mature cell types. (Photomicrograph by Russell Fletcher, UC Berkeley)

A rose may smell as sweet by any name, but for those without a sense of smell a rose by any name still smells like cardboard. Now there’s a glimmer of hope for those whose fine wine and roses are odorless and who can’t taste. Researchers at the University of California, Berkeley have found a gene that’s responsible for prodding stem cells in the nose to form new odor-sensing neurons.

A press release by Robert Sanders at the UC Berkeley quotes lead researcher John Ngai talking about the loss of smell in old age:

The release goes on to quote Gary K. Beauchamp, director of the Monell Chemical Senses Center in Philadelphia, who was not a member of the research team. He noted that the olfactory system stands out for its ability to regenerate following injury or certain diseases.

The group found a gene that seemed to be involved regulating nasal stem cells. They created mice that lacked that gene and found that the mice had more than the usual number of odor-sensing cells. Sanders goes on to write about how regulating this gene — called p63 — could help people regain a sense of smell:

Any real world result of this work would be many years off — the path from a mouse lacking a gene to a drug that’s available to humans is a long and arduous one.

Neuron, December 8, 2011
CIRM Funding: Russell B. Fletcher, Melanie Prasol (T1-00007)

A.A.