Cracking down on stem cell companies

Cross-posted from In the Field for Elie Dolgin

The International Society for Stem Cell Research (ISSCR) has convened a new committee tasked with weeding out companies that offer unapproved stem cell ‘therapies’, the ISSCR’s new president Irving Weissman announced today at the World Stem Cell Summit in Baltimore, Maryland.

See also an analysis of why unproven, risky stem-cell procedures elude legal restrictions in countries like China, India, Thailand, and the United States.

Last month, Weissman, who also directs the Stanford Institute for Stem Cell Biology and Regenerative Medicine in Palo Alto, California, wrote an opinion article in Cell Stem Cell calling for stem cell purveyors to be judged on three criteria. First, the company should be able to cite peer-reviewed papers from third party investigators showing that the therapy is possible. Second, there should be institutional review board oversight of the treatment. Third, the US Food and Drug Administration or an equivalent agency should give the final green light. “That’s the minimum beginning,” he said at the meeting.

Weissman revealed that he had convened an 18-member panel of lawyers, FDA regulators, medical ethicists, and stem cell scientists last week to look into the feasibility of establishing an online registry of wayward companies. His idea is for the ISSCR supervisory body to request documentation of the three requirements from all known global stem cell providers. Companies that don’t comply would get blacklisted.

Weissman expects the committee to issue a preliminary report in December, with final guidelines published next March.

Image of Weissman by Kris Novak

See an interview Irving Weissman: culturing the unorthodox

New stem cell bill in Congress?

Cross-posted from In the Field for Elie Dolgin

After the fanfare surrounding President Barack Obama’s executive order on 9 March, which lifted Bush-era restrictions on funding human embryonic stem cell research, the White House has been noticeably quiet about further expanding the science — one of Obama’s campaign promises. “We need to remind the President of this type of research,” Delaware congressman Michael Castle (Republican) said today at the World Stem Cell Summit in Baltimore, Maryland, the fifth annual summit presented by the non-profit Wellington, Florida-based Genetics Policy Institute.

Castle, together with Colorado congresswoman Diana DeGette (Democrat), previously introduced two bills to expand researchers’ access to human embryonic stem cell lines. Both bills were approved by Congress but vetoed by former President George W. Bush. Now, both House Representatives are at it again, working on new legislation to augment the executive order and prevent potential policy reversals from future residents of 1600 Pennsylvania Avenue. “I don’t like to see science subject to the whim of politics at all,” said Castle, who is also working to overturn the Dickey-Wicker amendment, which forbids the creation of embryos for research purposes on the taxpayer’s dime.

The bill is unlikely to brought before Congress anytime this year, however. Olivia Kurtz, Castle’s senior legislative assistant, told me that Castle and DeGette hope to roll out the bill before the current Congress’s term ends in January 2011. In the meantime, they are watching what happens with the National Institutes of Health’s expanded guidelines to identify potential shortfalls in the executive order that need remedying. Castle singled out nuclear cloning — the technique that produced Dolly the sheep — as one line of research that deserves further attention.

FDA green lights stem-cell clinical trial for Lou Gehrig’s disease

The Maryland company NeuralStem has the U.S. Food and Drug Administration’s permission to test its spinal cord stem cells in twelve patients with amyotrophic lateral sclerosis. The approval comes a month after the FDA placed Geron’s planned clinical trial on hold for a second time. NeuralStem’s trial had also previously been placed on hold by the FDA in February before receiving the go-ahead in September.

Though both trials involve placing cells into the spinal cord, NeuralStem’s product is made of cultured neural stem cells derived from a single 8-week fetus; Geron’s product, intended to treat spinal cord injury, is derived from embryonic stem cells that have been differentiated into precursors of neuron-support cells.

“This is certainly the first stem-cell approach for ALS,” says Lucie Bruijn, a scientist at the ALS Association, a patient group that also funds relevant research. Most other approaches for treating ALS are small molecule drugs, she says, and she’s not aware of other cell therapy or other invasive approaches entering human testing in the near future.

ALS has not funded NeuralStem’s work directly, Bruijn says, but has advised the company and funded academic scientists who’ve been involved with the company.

NeuralStem’s chief scientific officer Karl Johe says tests of large animal models show that the transplanted cells exert a neuroprotective effect over motor neurons, but it’s not entirely clear how. Earlier this year, Neuralstem and collaborators published results in a rat model of ALS showing that transplanted cells could develop into interneurons that formed synapses with the rats’ motor neurons.

However, Johe emphasized that the upcoming trial will assess safety rather than efficacy. The first few patients selected for the procedure will be those who are no longer able to walk. Because the injected cells protect rather than replace motor neurons, these sicker patients are less likely to benefit from treatment, but they are less able to lose function if something goes wrong. Cells will be injected only on one side of the spinal cord in order to minimize the number of injections into the spinal cord. Only one patient will be injected each month, so that researchers can monitor for effects over a longer period. Eventually, Johe says, the goal is to be able to inject cells in both lower and upper regions of the spinal cord in healthier patients, and see if the injections can keep motor neurons healthy.

The trial is expected to take place at Emory University in Atlanta, Georgia. Though the FDA is allowing the trial to go forward, the university’s patient-safety board will also need to approve the trial before it can proceed. Johe declined to say when that would be but said discussions were well underway.

Other companies using neural cells include ReNeuron, which received permission from UK authorities this January to start clinical trials for stroke. Its cell product is made from genetically modified cultures of neural stem cells, also of fetal origin.

StemCells Inc is conducting trials in Batten’s disease, a neurodegenerative disease that strikes children, and recently received approval for a clinical trial for a similar disease. It also uses neural stem cells from material originally derived from fetuses and has recently published results showing that its cell product delayed some symptoms of the disease by about three weeks.

As with human embryonic stem cells, the patent situation for neural stem cells is contentious. In a pair of dueling press releases this May, NeuralStem and Stem Cells Inc both claimed key intellectual property on these cells.

Submit your stem cells

By Elie Dolgin, cross-posted from the Great Beyond

stem_cell_colony03-m_M.jpgThe National Institutes of Health started accepting applications today to evaluate which human embryonic stem cells will be eligible for federal dollars.

A panel of nine scientists, lawyers and ethicists — led by Jeffrey Botkin of the University of Utah — will scrutinize submissions to ensure that they meet the new requirements for informed consent from embryo donors. The working group’s “expertise and sound judgment will help NIH move forward in this important effort,” NIH director Francis Collins, who will have the final say on the eligibility of particular lines, said in a statement.

The panel will review cell lines made before the guidelines went into effect on 7 July. Fundable lines must be derived from leftover embryos that were created solely for assisted reproduction and donated voluntarily with no financial incentives.

“We’re open for business in a new era,” Lana Skirboll, director of policy at NIH, told Nature. The working group has not yet appraised any cell lines — including the 21 lines approved under former President George W. Bush, which will need to be reassessed — and will start considering particular cells after scientists submit their petitions on the NIH website. “The speed at which this moves is really in the hands of the scientific community at this point,” she said.

Having a mechanism in place to expand the number of eligible cell lines “is what we’ve been working toward for a very long time,” said M. William Lensch, a stem cell researcher at Children’s Hospital Boston and the Harvard Medical School, who expects to start submitting requests “sooner rather than later.”

Image: James Thomson, University of Wisconsin-Madison

Editor’s note:

(See related story: An analysis suggesting that the NIH did not properly evaluate informed consent by donors of embryos from which stem cell lines were derived throw oversight committees into disarray )

Also, see below a list of the other members of the panel and for links to a critical analysis of the ethical review conducted under President George W. Bush’s administration.

Read more

CIRM signs agreement to collaborate with Germany on stem cell research

The California Institute of Regenerative Medicine has collected a sixth country for its international collaborations. German and Californian scientists will be able to submit joint grants for collaborative projects that focus on immunology. Researchers would, however, be funded by their respective governments.

(See CIRM’s melting pot of collaborators)

At a signing ceremony in CIRM’s office in San Francisco, the German Federal Ministry of Education and Research, Freider Meyer-Krahmer described the new memorandum of understanding as opening up “totally new ways of collaboration” with perhaps three or more countries coming together. “Not just the researchers but also the funders collaborate.”

CIRM president Alan Trounson said the agreement grew out of past meetings between German and Californian scientists who had identified ways that they wanted to work together, particularly on ways to understand how transplanted cells will interact with patients’ immune system. Officials declined to state the amount of funds that would be involved, but Trounson said that governments must commit a certain minimum amount of funds, on the order of $1 million to $2 million dollars to “make the paperwork worthwhile.”

The officials said that the collaboration would avoid duplication and allow researchers to capitalize on advantages within both jurisdictions. Both Trounson and CIRM chair Robert Klein praised German work conducting large clinical trials in adult stem cells.

Each government will conduct their own ratings of the submitted grants, said officials, but they would establish a mechanism to make sure that both CIRM and German granting agencies would be awarding grants to the same teams.

CIRM plans to pursue additional agreements in the near future, particularly with U.S. state governments that have allocated funds to stem cell research. Agreements are already in place with Australia, Canada, Japan, Spain, and the United Kingdom.

Reply to question about cell therapies for diabetes

I recently got this query in my inbox: I would like to know how to find research trials on the reprogramming and induced pluripotent stem cells. My son was diagnosed three years ago with type l diabetes and his doctor believes that he would be a good candidate for one of these research trials. How do we go about finding these research trials and what do we need to do to get him involved, David is 21 years old. Any help would be greatly appreciated as he would like to help further research and end diabetes.

Here’s my reply. If anyone wants to add something, send it in to the comments, please. Thanks.

Hi, You can find diabetes trials by going to clinicaltrials.gov. The portal http://clinicaltrials.ifpma.org/no_cache/en/myportal/index.htm lists more trials outside the US, but I find it harder to use.

There aren’t any clinical trials going on in diabetes with iPS cells yet. IpS cells have only very recently been differentiated into the relevant cells (Melton in PNAS), and these cells still have to be more fully characterized.(See this from Technology Review) There is some mouse work using genetic engineering to convert pancreatic cells into the insulin-secreting, glucose responsive beta cells that are lost in diabetes, but it is a very long way from a genetically engineered mouse study to a human trial. (See Smash the (cell) state and A sort-of beta cell magic )

Novocell and the Juvenile Diabetes Research Foundation are looking at cell therapies, so is NovoNordisk; you might want to get on their mailing lists. Also, you might want to read our feature Diabetes stem-cell treatment looks to cell capsules which lists several companies and researchers working in this space. (These lump iPS and ES cells together, but the ES work is much further along than the iPS work)

Good luck.

Big list publications from the last big stem cell meeting

Listening to scientific talks makes me nervous; it’s so easy to conflate and confuse fast-flowing information. At the most recent meeting of the International Society for Stem Cell Research (ISSCR) this July in Barcelona, I frequently found myself wishing for the slower pace of reading the relevant source material. Others must also want such a list, I reasoned. So, with a great deal of help, and no little cutting and pasting, Nature Reports Stem Cells put it together.

It necessarily lacks all the as-yet-unpublished work presented, but I hope it still provides a valuable snapshot of the work going on in July 2009. the link to the formatted list is below, and I hope that people in the stem cell community will round out what is missing via comments. Thanks for your work.

The 7th ISSCR reading list compiles work that has been published and accepted (and whose scientists told me about it)

Here are the Niche’s own blogs from the ISSCR meeting

Last thoughts on ISSCR: thanks to guest bloggers and congrats to poster winners

p53 at ISSCR: not just for cancer anymore

ISSCR 2009 meeting: what’s changed from last year?

ISSCR sessions from Barrandon and Mikkola: thymus makes skin, SCL starts up HSCs

ISSCR Friday posters: cell-penetrators, differentiators, memory-storers, and more

Business round-up: pluripotent products, all-star academics and headlines everywhere

ISSCR plenaries: how to repair 1) a salamander leg and 2) a human airway

ISSCR posters: In vitro stem cell culture: are we doing enough to make the cells feel at home?

ISSCR session: Consistent differences in ES and iPS cells

Why Yamanaka’s new results don’t (necessarily) spell doom for most human iPS cells

Thursday at ISSCR

Congratulations to John Gurdon and Shinya Yamanaka on the Lasker Prize

http://www.genengnews.com/specialreports/sritem.aspx?oid=62812927John Gurdon of Cambridge University and Shinya Yamanaka of Kyoto University have been awarded the Lasker prize, also called the American Nobel. (I imagine anyone reading this blog already knows who they are.: frog cloner and cell reprogrammer)

See the report in Bloomberg

Genetic Engineering News has a special report

See a profile of Shinya Yamanaka from the Nature Reports.

This week in stem cells

On Nature Reports Stem Cells and Nature News

News

Ethics scrutiny needed for Chinese-European projects

Panel calls for joint advisory body to monitor research.

Stem-cell drug fails crucial trials

Experimental treatment does not halt fatal complication of bone-marrow transplant.

Stem cell company accused of hype

Strong words from the SEC

News and highlights from recently published papers

International Stem Cell Research Society reading list, a compilation of papers presented at ISSCR

Induced pluripotent stem cells down to one factor

Human neural stem cells reprogrammed with only OCT4

What does Nanog do?

In embryos and induced pluripotent stem cells, Nanog sets the ground state of pluripotency

Stem cells delay disease onset in mice with neurodegenerative disease

Transplanted cells from biotech company detoxify poisoned brains, at least for awhile

Research papers and perspectives

A luminal epithelial stem cell that is a cell of origin for prostate cancer from Michael Shen at Columbia University and colleagues

The story was reported, among other places, in Reuters. Here’s the press release.

Developmental biology: Instructions writ in blood by Tariq Enver and Sten Jacobsen at University of Oxford

Cancer stem cells: mirage or reality? by Robert Weinberg at the Broad Institute and colleagues

Systems biology of stem cell fate and cellular reprogramming by Ihor Lemischka and colleagues at Mount Sinai School of Medicine

Stem-cell company charged with hype

963-CellCyteLogo.jpg

By Elie Dolgin

Cross-posted from The Great Beyond

US regulators accused a stem cell biotech company on Tuesday of inflating claims about an early stage cell therapy.

The US Securities and Exchange Commission (SEC) charged Bothell, Washington-based CellCyte Genetics Corporation, along with its former chief executive and former chief scientific officer, with duping investors into believing that its experimental stem cell technology was nearing human trials.

“CellCyte and its senior officers knew that it would take years of research to determine whether the stem cell discovery could be developed into a viable product,” said Marc Fagel, director of the SEC’s San Francisco office, in a statement. “In their rush to cash in on the promise of stem cell research, they concealed the true facts from investors.”

In 2005, CellCyte licensed a compound that had been shown in preliminary animal studies to help stem cells migrate to specific organs of the body. Cellcyte’s own experiments failed to replicate these findings, according to the SEC’s complaint. Nonetheless, the company claimed in 2007 that it had received U.S. Food and Drug Administration (FDA) approval to begin human clinical trials to repair heart damage even though CellCyte had never filed an investigational new drug application. The company also falsely claimed that its drugs improved bone marrow engraftment, the SEC charged.

In truth, the SEC alleges, “CellCyte did not know how to properly formulate the stem cell compound, had never attempted experiments with the compound to repair organs, and had not satisfied any of the FDA requirements to begin human clinical trials.”

In autumn 2007, CellCyte partnered with a stock promoter to nearly double its share price from $4.00 to $7.50 over the span of four months. The stock now trades for about a nickel.

CellCyte blamed the mix-up on the US Department of Veterans Affairs (VA), from whom the company licensed the stem cell technology. “Once we realized the technology didn’t do what the VA told us it would do, we discontinued working on that technology,” Randy Lieber, CellCyte’s acting chief financial officer, told The Scientist.