Researcher Alert: CIRM Readying $57 Million in New Opportunities

The California stem cell agency is proposing to pump $30 million into new research involving reprogrammed adult stem cells and another $27 million into fresh efforts to speed development of clinical therapies.

In a memo prepared for the CIRM directors meeting next week in Los Angeles, the agency's staff said the $30 million effort could generate "disease-in-a-dish models" that "have the potential to make drug discovery faster, more efficient and more personalized to individual patients."

The "disease-in-a-dish" plan was dubbed a "human pluripotent stem cell (hPSC) initiative" by the staff. The goal is to generate high quality stem cell-based tools for use by the researchers and drug developers.

The proposal includes four elements, one of which is collaboration with the NIH to develop cell lines from patients with Huntington’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis. No cost was specified on that effort. Also recommended to directors was a $4 million disease line award round, a $16 million core hiPSC derivation round and a $10 million stem cell bank round. The RFAs would go out in May of next year with funding expected early in 2013.

The staff memo on the initiative did not mention human embryonic stem cells, but a spokeswoman for the agency said they were not excluded from the effort.

The other new grant proposals up next week grew out of a recommendations from a blue-ribbon panel that CIRM organized last year to examine its operations. One element in the plan is a $12 million "bridging fund" that would apply only to current CIRM-funded projects in three areas: disease team grants, some early translational projects and clinical development projects. The bridging fund would provide up to $3 million for up to one year for each recipient, if CIRM President Alan Trounson approves the project. Trounson would be assisted in his evaluation by staff and external consultants, if necessary.

The second part of the response to the review panel's finding is an "external innovation initiative" to support collaborative efforts of CIRM grantees to work with teams that CIRM said are "making extraordinary progress outside California."

The $15 million program would provide awards as often as two times a year. The maximum amount on each award was not specified.

Ellen Feigal, CIRM's vice president of research and development, said in a memo to directors that examples of potential projects included collaborative efforts with the NIH and work with the Harvard Stem Cell Institute and its disease-focused programs.

Some of the latest CIRM initiatives are open to biotech businesses. Others are open only to non-profit or academic researchers.

(Editor's note: An earlier version of this item did not include the sentence dealing with human embryonic stem cells.)

Questions and Commentary on Stem Cell Reprogramming

The California stem cell agency and a UC Davis stem cell researcher are blogging on the implications of research that indicates that reprogrammed adult stem cells may not be the magic bullet that avoids the problems associated with human embryonic stem cells.

You can find a summary of some of the research and discussion from CIRM's Amy Adams here. Paul Knoepfler of UC Davis said,

"So if iPS cells are not that similar to ESC, what does this mean?

"First, it is not the end of the world. Many of us had assumed that iPS cells are similar to ESC in some ways, but distinct in others. These studies simply validate that notion.

"Second, iPS cells are still very useful even if they are not quite so close siblings of ESC. In fact, iPS cells do not need to be extremely similar to ESC to be useful. The pluripotency and self-renewal of iPS cells makes them a powerful tool regardless.

"Third, iPS cells are a distinct type of stem cell from ESC and should be considered as such.

"Fourth, these studies also highlight that every iPS cell line made is distinct from the others made. The heterogeneity amongst iPS cell lines is probably more substantial than the differences between ESC lines, but ESC lines also vary between each other quite a lot as well.

"Finally, the tumorigenicity of iPS cells is a serious concern. A remaining open question is how prone iPS cells are to form malignant tumors (although don't forget that teratoma can be malignant!). We predict that iPS cells are dramatically more prone to produce malignant tumors compared to ESC."

(Editor's note: An earlier version of this item contained typos in the material that was inserted from Knoepfler's original post. He corrected those typos on his blog, and we have altered his quote above to reflect those changes.)

Reprogramming and Unicorns

CIRM President Alan Trounson has weighed in on some of the issues that attend the reprogramming of adult stem cells.

In a piece in the December 2008 issue of Cell Stem Cell entitled "Rats, Cats, and Elephants, but Still No Unicorn: Induced Pluripotent Stem Cells from New Species," Trounson noted that reprogramming is likely to attract attention from animal conservationists trying to preserve endangered species.

On the human front, he wrote,

"No matter how similar mouse, rat, and human iPSCs might be, it remains to beseen whether the usefulness of human iPSCs can be established, given the presence of viral sequences and of multiple copies of the transcription factors in potentially unregulated sites in the human genome. Regulatory agencies are likely to consider these lines to be genetically engineered and will consequently hold them to a very high bar in order to establish safety for use in human therapy. On the other hand, the potential availability of riPSCs for modeling human diseases will be very attractive to researchers and companies involved in drug discovery, as the mouse has often proven inadequate as a model for candidate therapeutics."

Margolis: Beware the Embryonic Cheerleaders

The Stem Cell Blog run by Stanford's Chris Scott carried an interested commentary the other day from Don Margolis, founder of the adult stem cell company, VesCell, who tackles some of the issues related to reprogramming of adult stem cells.

Among other things, Margolis invokes cancer, criticizes "embryonic cheerleaders" (presumably not unborn pom-pom girls) and attacks "censorship" of those who differ with the heralds of hESC.

Margolis also hails the "refreshing" honesty of such folks as Jamie Thomson, George Daley, Doug Melton and Shinya Yamanaka. You can find the piece here.

CIRM To Bush: Harmful and Wrong

The California stem cell agency is accusing President Bush of distorting facts and performing a disservice to millions of Americans who suffer from chronic diseases and injuries.

The agency said Bush intends to "further limit" research into human embryonic stem cells.

The CIRM statement is contained in a press release on its web site that concerned Bush's speech Tuesday night. Interestingly, the CIRM statement is not attributed to either Bob Klein, chairman of the agency, or its new president, Australian stem cell researcher Alan Trounson. In the past, statements such as this have been linked to either the president or chairman.

Here are excerpts from the release followed by the two paragraphs from the president's speech.

"President Bush distorted the scientific facts on stem cell research and did a disservice to the millions of patients suffering from chronic disease and injury for whom stem cell research holds great promise for future therapies and cures."

"The President’s proposals to further limit medical research in this area fail to take into account the intricate realities of the state of stem cell research. Indeed, the recent advances in which skin cells were induced to become pluripotent would not have been possible without research involving human embryonic stem cells."

"Therefore it is critical that all avenues of stem cell research be aggressively advanced. To do otherwise would increase the already devastating restrictions that have burdened Federal support of stem cell research and patients who are depending upon it. This Administration’s position on stem cell research has already cost years in lost research productivity. Further restrictions would result in more lost time in developing stem cell based therapies and cures that hold great promise to alleviate suffering for the most destructive and costly diseases such as spinal injury, loss of sight, heart muscle injury, Parkinson’s Disease, ALS and diabetes."

Bush's comments:

"On matters of life and science, we must trust in the innovative spirit of medical researchers and empower them to discover new treatments while respecting moral boundaries. In November, we witnessed a landmark achievement when scientists discovered a way to reprogram adult skin cells to act like embryonic stem cells. This breakthrough has the potential to move us beyond the divisive debates of the past by extending the frontiers of medicine without the destruction of human life.

"So we're expanding funding for this type of ethical medical research. And as we explore promising avenues of research, we must also ensure that all life is treated with the dignity it deserves. And so I call on Congress to pass legislation that bans unethical practices such as the buying, selling, patenting, or cloning of human life."

Stem Cell Snippets: Toes, Public Support and Looking Forward

WSJ on Stem Cells – Columnist Robert Lee Hotz wrote today in the Wall Street Journal about non-federal stem cell research efforts and reprogramming of stem cells. He quoted Richard Murphy(see photo), interim president of CIRM, as saying that research on human embryonic stem cells must continue. "We need to sort out the realities," Murphy said. The piece also contained a forward-looking number that is increasingly turning up in articles involving CIRM. That is the figure of $519 million, which is what CIRM expects to have approved for stem cell research by the middle of this year.

Bad Poll Numbers – "Strong support" is declining for human embryonic stem cell research, according to a recent poll by the Virginia Commonwealth University. The survey was taken following the latest news on reprogramming of adult stem cells. According to a piece by A.J. Hostetler of the Richmond Times-Dispatch, "strong support" peaked in 2005 at 27 percent and has now fallen to 21 percent. Overall support remains at 54 percent. It is the first national poll taken on stem cell research since the announcement of the reprogramming studies in November.

Murphy's Toe? – Reporter Ron Leuty of the San Francisco Business Times put together a bit of an overview of CIRM recently. The main focus was on the conflict of interest problems at the agency. He quoted Richard Murphy as saying, "We stubbed our toe. We all didn't realize we had a problem here." Michael Fitzhugh of the East Bay Business Times also looked at the impact of CIRM activities on companies in the eastern area of the San Francisco Bay region. If you have difficulty obtaining full copies of the articles, please send a request to djensen@californiastemcellreport.com, and we will send them to you.