ACT files to test embryonic stem cell-based therapy for macular degeneration

Advanced Cell Technology has filed an application with the FDA to begin an early phase trial of an embryonic stem cell-based therapy for macular degeneration. If the company name sounds familiar, that’s because it’s the same company that on November 22 received FDA approval to begin a trial for Stargardt’s macular degeneration. Both trials are testing the same cells. In a press release, the company said:

Company scientists view the use of the same hESC derived RPE cells for both trials as the most efficacious approach, as it permits the Company to leverage its experience with the FDA that it gained through the process of obtaining approval for the Stargardt’s clinical trial to expedite the approval of its clinical trial in Dry AMD.

As with the company’s Stargardt’s trial and Geron’s spinal cord injury trial, this new trial will be assessing safety in a very small number of patients — standard practice for any new therapy being tested. After proving safety in a phase I trial, a larger trial will assess whether or not the potential therapy is effective.

It’s exciting to see embryonic stem cell derived therapies reaching patients. In general, more trials fail than succeed and we don’t know in advance which ones are going to work. That’s why there are hundreds of cancer trials going on around the country, and why we need hundreds of stem cell trials too. Hopefully CIRM’s macular degeneration disease team led by Mark Humayun at USC won’t be far behind ACT with their own version of an embryonic stem cell-based therapy for macular degeneration. And hopefully, one of them will provide a cure for the roughly 30 million people worldwide who are losing or have lost vision due to the disease.

Here’s a video about the CIRM disease team project:

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A stem cell by any name

This past year has brought a number of advances in creating reprogrammed iPS cells and in directly reprogramming mature cells into a different cell type. With each advance comes the question: Where does this leave embryonic stem cells? And each time, stem cell scientists remind us that the advances are great and could potentially lead to exciting therapies, but there’s a lot to learn in terms of safety.

An AP story today has a great quote from George Daley of Children’s Hospital Boston and the Harvard Stem Cell Institute, whose lab has been responsible for many of those advances:

When we make a duck look like a cat, it may look like a cat and meow, but whether it still has feathers is an issue.

It was a good weekend for analogy. CIRM grantee Paul Knoepfler at UC Davis came up with this one on his blog:

If ES cells are like a safety and road tested Ford (a model that’s been around a dozen years), then IPS cells are a shiny new sports car that even the experts know very little about. We are not sure how its accelerator or brakes work. It hasn’t been crash tested. It looks really fast and everyone thinks it has a lot of potential, but it’s only been around a very short time.

If you had to get you and your loved ones safely from point A to point B, which kind of car would you go in at this time?

IPS cells have outstanding potential, but they are still somewhat of a mystery, particularly in terms of their safety. I predict that in a few years, there will be safe iPS cells, but we aren’t there yet. We just don’t know enough.

A comment on Knoepfler’s blog points out:

I would say that adult stem cells are cadillacs: been around a long time, you know what you are getting, solid

Depending on which analogy you prefer, CIRM funds either an entire zoo, or a full parking lot. Here’s my own analogy: Some diseases are more like mountain passes and require a sure-footed SUV. Others are winding highways ideal for racing. CIRM grantees are test-driving all types of stem cells with the goal of learning which provides the best transportation to a cure for different diseases. If all we have are Cadillacs we’ll have a hard time with diseases that require a space-saving Smart car.

You can filter our list of all funded stem cell research awards according to the stem cell type being used.

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Sherley vs. Sebelius and the redefinition of "research"

The Sherley vs. Sebilius case that has put human embryonic stem cell research on pause throughout the country has an interesting new twist. According to ScienceInsider the Boston Biomedical Research Institute, which employs James Sherley, one of the two scientists who sued to block federal funding for human embryonic stem cell research, has joined the pro stem cell side. They filed a motion explaining the many ways BBRI researchers intend to use human embryonic stem cells in the future.

That case is due to be heard December 6 and has a number of key scientific leaders in addition to the BBRI weighing in on the side of the NIH. The University of Wisconsin filed an amicus brief, which both the Genetics Policy Institute and the Coalition for the Advancement of Medical Research asked to join.

There’s one interesting aspect to the case that hasn’t received much attention. It came up in an amicus brief filed by the regents of the University of California. The brief, which is remarkably entertaining reading (no really), makes the point that the case would fundamentally redefine what is meant by a piece of “research.” The logic goes like this:

  • The plaintiffs argue that the Dickey-Wicker Amendment prohibits the destruction of human embryos (so far so good).
  • And that deriving new human embryonic stem cell lines from IVF embryos does, in fact, destroy the embryo (still good — this is why the NIH can’t fund the creation of new lines)
  • And that since human embryonic stem cell research requires using stem cell lines that once resulted in the destruction of an embryo, that work also can’t be funded by the NIH (huh?)
  • So, a piece of a research in a proposal to the NIH includes not only the proposed work, but everything that came before it.

The UC Regents brief had this to say:

If an activity is included within the proposed project and is funded by the NIH grant, then, by definition, that activity is part of the funded research. If the activity is not included in the request for funds, no NIH funds are made available for that activity, no NIH grant funds are used for that activity, and, by definition, the activity is not part of the funded project. Thus, if grantees do not request funds for the derivation of hESCs or the creation of hESC lines and NIH does not award funds for those activities, by definition, NIH has not funded any research in which embryonic stem cells are derived or propagated.

(Emphasis added)

So, by the logic of the plaintiffs, if a researcher proposes carrying out research with iPS cells that follows up on knowledge gained from work with embryonic stem cells, is that iPS work also the indirect result of a destroyed embryo and therefore not fundable by the NIH?

It doesn’t make a lot of sense.

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Vision loss trial based on embryonic stem cells begins

The FDA has given the green light to the second trial based on embryonic stem cells — this one for a genetic form of blindness called Stargardt’s Macular Degeneration. The treatment, developed by Advanced Cell Technology, involves replacing the the layer of the retina damaged by the disease, called the retinal pigment epithelium, with new RPE cells derived from embryonic stem cells.

This approach is similar to one under development by a CIRM macular degeneration disease team led by Mark Humayun at the University of Southern California.

Nature wrote about the ACT trial:

In the trial, 12 individuals at several US medical centres will receive injections of the cells directly into the eye to test the safety of the procedure. (Although the disease begins to take its toll at around 6 years of age, the trial will start with patients who are over 18.)

The small size of the trial is typical for a Phase I/II trial, which is primarily looking to ensure that the technique is safe before testing it in more people. Nature went on to quote ACT’s chief scientific officer Robert Lanza:

The advantage, of course, is that we’re talking about a very small number of cells going into a very local area,” he says. Using instruments that can track a single retinal cell in the eye in real time, the researchers will also be able to easily monitor patients’ progress.

“Also, with the eyes there are very objective tests for visual acuity,” he notes, “so we can measure performance gains very objectively.” Tracking improvement after spinal cord injury, on the other hand, is notoriously tricky.

This video features Mark Humayun discussing his macular degeneration work:

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Rock stars of science: making science cool

There’s been a lot of discussion recently about explaining science to the public, capped by GQ photo shoot featuring scientists and rock stars as part of the Rock Stars of Science campaign. I was happy to see our own Catriona Jamieson of UCSD featured with British singer-songwriter and rapper Jay Sean.

According to a story in The Scientist:

Since the campaign was launched, nearly 250,000 people have visited the Rock Stars of Science website. Videos of the Rock Stars Hill briefing on September 24, 2009 were seen by more than 4,500 people, according to Research!America. And the events have attracted media attention. For example, ABC gathered some scientists from the 2009 Rock Star campaign in a panel on Alzheimer’s on Nightline.

A few big name scientists seem impressed:

Anthony Fauci, director of the National Institute of Allergies and Infectious Diseases and 2009 Rock Star Scientist, said he’s gotten feedback that suggests the campaign helps encourage young people to contemplate careers in science. “The message was that you can get the same thrill and rush from science as you can from being a rock star,” he said, “so from my point of view it was a home run.” Collins, another rock star alum, said in an email he thinks the campaign is a “terrific” vehicle to excite kids. “The effort aims to show scientists as a very cool part of our culture,” he said. “Kids need to know that you don’t have to be a total geek to be a great scientist.”

At the same time, Nature recently ran a piece giving scientists some how-tos when it comes to talking about their work. Because it doesn’t do any good to be a rock star of science if you can’t effectively explain what your scientific progress to the public, to law-makers and to science skeptics. The Scientist describes the much-feared Sagan effect that might be preventing scientists from communicating more passionately about their work:

Some worry that media interaction can taint careers. The ‘Sagan effect’, named after the astronomer and famous science communicator Carl Sagan, suggests that frequency of media interaction might be inversely proportional to scientific ability. Sagan’s biographers, Keay Davidson and William Poundstone, both say that his popularization of science was a big reason that the National Academy of Sciences did not accept him as a member. And yet Sagan, as they document, had a prolific publication record and many protégés, including Squyres.

Finally, CIRM grantee Paul Knoepfler had this to say about why scientists should quit worrying about perception and start talking to the public. He wrote a blog entry about the need for scientists to get with the times in terms of communicating electronically. In a follow-up comment to his blog entry he wrote:

Scientists need to communicate in real time, or as close to it as possible, on the Internet. If they choose not to or are simply so unaware that they don’t even know they should be doing this, they have lost out on an opportunity to not only to educate, but also to advocate. The anti-science groups out there have learned this lesson well.

CIRM held a media training at our annual grantee meeting last year in an effort to help grantees talk about their work. With all the misinformation about stem cells — regarding their origins and their therapeutic power — we need as many scientists as possible able to talk effectively about their findings.

Those rock stars of science communication might never have the name or image recognition as Debbie Harry or Bret Michaels, but we do hope they can be part of an effort to help people understand the power of science to create new therapies or technologies that improve our world and our lives. And to explain that science is just plain cool.

Both Jamieson and Knoepfler have been very effective communicators of stem cell science. In addition to other media work, they both worked with CIRM to create explanatory videos:

Paul Knoepfler: Tumor Formation in Embryonic Stem Cells
Catriona Jamieson: Therapies Based on Cancer Stem Cells 

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Top four list: why embryonic stem cells are critical

Yesterday CIRM grantee Bruce Conklin gave his top four reasons why embryonic stem cells are so valuable and why federal funding for the work needs to be able to continue. Conklin, who is Senior Investigator Gladstone Institute of Cardiovascular Disease and professor at UCSF, studies heart rhythm defects by creating iPS cells from people genetically predisposed to have those defects, then maturing those into heart cells in a dish. This gives him a way of studying the rhythm defect in the lab, and allows him to test drugs that might correct the arrhythmia. (You can see his New Cell Lines Award research summary here.)

Conklin says he’d never be able to carry out his iPS work without advances made with embryonic stem cells. Here’s his list:

1) Scientists have genetically engineered embryonic stem cells that are widely used for studying specific processes in the lab. “Obviously, we can remake those cells lines using iPS cells but it’s a huge waste of time,” he said. Instead of making progress toward developing new therapies or finding new drugs, labs would have to spend years redoing work they’ve already done.

2) Embryonic stem cells are farther along clinically than iPS cells or the new directly reprogrammed cells. “The first clinical trials of pluripotent cells will be embryonic stem cells. Ten years from now we’ll probably see a mix of embryonic and iPS cells,” he predicted. Adult cells are good for many things, he said, but aren’t as flexible as pluripotent embryonic or iPS cells.

3) Embryonic stem cells reproduce the steps taken by nature. “The idea is that nature knows something we don’t, because we don’t know very much,” Conklin said. Studying embryonic stem cells as they go down the path toward a specific cell type, like a skin cell or a neuron or a pancreatic islet cell, can give us clues about what might be going wrong in diseases afflicting those cell types.

4) Some diseases seem to begin at the earliest stages of development. “If we are going to understand human development we have to know how the process happens naturally,” he said. Only by studying embryonic stem cells can we understand genetic diseases that strike at the earliest stage, or what’s called epigenetic changes that can alter the way genes function.

Conklin seemed optimistic about the future of iPS and direct reprogramming, but pointed out that even Jamie Thomson, who was part of one of the two teams that first created iPS cells, has predicted that iPS cell research would be five years ahead of where it is now if embryonic stem cell research weren’t slowed under the Bush funding regulations.

The CIRM Governing Board recently passed a resolution that “strongly encourages federal policy that supports all forms of stem cell research for the millions of Americans who suffer from disease and injury and strongly supports criminalizing human reproductive cloning.” You can read Resolution 2010-01 here, which supports both the DeGette and Spector legislation “or any successor legislation that embodies the policies advanced in President Obama’s Executive Order 13505 and the National Institutes of Health July 7, 2009 guidelines on hESC research.”

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Mighty mice point to stem cell therapy for muscle diseases and aging

The L.A. Times gave it’s rodent of the week designation to a mighty mouse produced by University of Colorado, Boulder researchers.

The group transplanted muscle stem cells from healthy mice into mice with damaged muscles. Not only did the muscle stem cells spring to action, repairing the damaged muscle, but they maintained the mouse in its newly bulked up state for its entire two-year lifespan.

The Telegraph quotes lead author Bradley Olwin as saying:

“We found that the transplanted stem cells are permanently altered and reduce the ageing of the transplanted muscle, maintaining strength and mass.”

“With further research we may one day be able to greatly resist the loss of muscle mass, size and strength in humans that accompanies ageing, as well as chronic degenerative diseases like muscular dystrophy.”

In their story, the L.A. Times points out that the stem cells came from young mice and were implanted into similarly young mice. Other research by CIRM grantee Irina Conby at University of California, Berkeley has found that the environment in older mice somehow inhibits muscle stem cells from repairing damaged muscle (here’s a blog entry on her work). Likewise, bathing muscle stem cells from older mice in the blood of young mice seems to rejuvenate the cell’s ability to repair tissue.

The issue of aging and environment is an important one when looking at transplantation of adult stem cells. Where the cells are implanted could play an important role in how well the cells repair damage. (You can read more about aging and stem cells in this story from Stanford University.)

As a runner prone to muscle damage and whose clock is relentlessly ticking, I’ll be watching for researchers to figure out what it is that allows the transplanted stem cells to flourish and prevent aging in mice. And I can only hope the answer is not that I have to remain young for my muscle stem cells to thrive.

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November 14: World Diabetes Day

Guest bloggers Chris and Lorraine Stiehl are CIRM Patient Advocate Coordinators*:

Sunday, November 14 is World Diabetes Day. Back in 2004, we joined the team that launched Prop 71 because of the opportunity that stem cells may provide for diabetes. We are now involved with CIRM as Advocacy Coordinators, working with all of you across the state to help bring the exciting research made possible by CIRM to the patient advocacy community. In our short time in this role, we have met many passionate and dedicated stem cell advocates who are working hard to find better treatments and cures for dozens of diseases.

In honor of World Diabetes Day, we thought we’d make diabetes the subject of our first blog posting. As you know, diabetes is a growing epidemic in California and across the globe. CIRM has funded numerous research projects involving diabetes including a Disease Team Research Award granted to UCSF and ViaCyte (you can see a complete list of diabetes awards funded by CIRM). Not only are these researchers seeking to create an unlimited supply of insulin-producing beta cells from stem cells, they are exploring ways to protect these cells from attack by the patient’s own immune system. Now that these researchers have experienced success in animal models, they are excited about moving their research into pre-clinical and clinical application – thanks to CIRM funding. This goal is in sight.

The Centers for Disease Control (CDC) estimates that there are over 24 million Americans who are living with diabetes. Approximately 3 million of these individuals have type 1 diabetes, the most severe form of this disease. Voluntary health organizations such as the Juvenile Diabetes Research Foundation (JDRF), a major funder of Prop 71, and the American Diabetes Association (ADA), continue to promote stem cell research and partner closely with organizations such as CIRM.

In addition to supporting research, JDRF and ADA work hard to create a platform for the diabetes community to organize itself, so advocates may more effectively advance research at both the state and federal levels of government. Websites such as www.tudiabetes.org and www.juvenation.org provide opportunities for those with diabetes to build relationships with one another and find daily support. Translating the deeper connections made possible through social media into offline relationships is also critical. That is why JDRF is hosting Type 1 Talk on World Diabetes Day, November 14. Additionally, ADA is actively promoting World Diabetes Day and their activities may be found on their website.

As Patient Advocate Coordinators for CIRM, we hope to educate, excite and empower advocates involved in all diseases that demand a cell-based solution such as those found in stem cell research. We look forward to working with all of you in the coming months And if you want to keep up with stem cell research more broadly become a fan of CIRM on FaceBook.

Lorraine Stiehl also serves as the National Chair of Grassroots Advocacy for JDRF and was their Volunteer of the Year for 2010. She will be one of the speakers on the Type 1 Talk webcast.

* This entry was updated 11/16 to reflect the proper title for Chris and Lorraine Stiehl: “CIRM Patient Advocate Coordinators”

Stem cell model of autism allows testing of new drugs

Back in May 2009, CIRM held a workshop in which leading scientists discussed ways in which stem cell research could benefit people with autism (here is the autism workshop report from that meeting). I have two friends with children who are on the spectrum and have seen first-hand the toll the disease takes on the families.

This week, some CIRM grantees published an exciting paper that reflects the hopes of that workshop. The scientists took skin cells from people with a severe form of autism called Rhett syndrome, reverted those cells to an embryonic state, and matured them into neurons. The work was published in the in the November 11 issue of Cell. This is the first time scientists have been able to study what amount to autistic neurons in a lab dish.

It turns out they have some abnormalities, as you might expect. According to Technology Review:

They found that neurons derived from patients with Rett syndrome showed certain abnormalities, including markedly smaller cell bodies, dendrite connections, and decreased cell-to-cell communication.

The best part is that when the team from the Salk Institute and the University of California, San Diego exposed these neurons to a protein called insulin-like growth factor the neurons looked more normal.

This type of work is precisely what the workshop recommended as a starting point. Nerves grown from people with autism are an ideal environment for testing possible therapies and for understanding the disease. The group hopes to test therapeutic options suggested by these findings in mice, and to grow neurons from people with different forms of autism.

At this point the work is far too early to benefit my friends. The scientists still need to better understand the different forms of autism, study this proposed therapy in animals and understand the mechanism better before they can even begin thinking about a human trial. But for a disease that currently has so little clinical hope, even early stage work is a step in the right direction.

CIRM funding:
Fred Gage (RL1-00649-1 and RC1-00115-1)

Nobel prize winner Stanley Prusiner calls for Alzheimer’s disease funding

Nobel Prize winner Stanley Prusiner was one of the authors on a letter to the New York Times on October 27 advocating that congress pass legislation that “would raise the annual federal investment in Alzheimer’s research to $2 billion, and require that the president designate an official whose sole job would be to develop and execute a strategy against Alzheimer’s.”

Prusiner, who is director of the Institute for Neurodegenerative Diseases at UCSF, along with retired U.S. Supreme Court Justice Sandra Day O’Connor and gerontologist/psychologist Ken Dychtwald, wrote:

As things stand today, for each penny the National Institutes of Health spends on Alzheimer’s research, we spend more than $3.50 on caring for people with the condition. This explains why the financial cost of not conducting adequate research is so high. The United States spends $172 billion a year to care for people with Alzheimer’s. By 2020 the cumulative price tag, in current dollars, will be $2 trillion, and by 2050, $20 trillion.

If we could simply postpone the onset of Alzheimer’s disease by five years, a large share of nursing home beds in the United States would empty. And if we could eliminate it, as Jonas Salk wiped out polio with his vaccine, we would greatly expand the potential of all Americans to live long, healthy and productive lives — and save trillions of dollars doing it.

Their letter came days after CIRM board member Leeza Gibbons joined California’s First Lady Maria Shriver in her first March on Alzheimer’s at the California Women’s Conference. Gibbons founded Leeza’s Place to provide support for caregivers of people with Alzheimer’s disease and other disorders. The march raised a quarter of a million dollars for Alzheimer’s research.

During Alzheimer’s disease awareness month here are some numbers to keep in mind, from the NYT letter:

Starting on Jan. 1, our 79-million-strong baby boom generation will be turning 65 at the rate of one every eight seconds. That means more than 10,000 people per day, or more than four million per year, for the next 19 years facing an increased risk of Alzheimer’s. Although the symptoms of this disease and other forms of dementia seldom appear before middle age, the likelihood of their appearance doubles every five years after age 65. Among people over 85 (the fastest-growing segment of the American population), dementia afflicts one in two. It is estimated that 13.5 million Americans will be stricken with Alzheimer’s by 2050 — up from five million today.

CIRM has a Alzheimer’s disease fact sheet about stem cell therapies for Alzheimer’s disease, and a list of all awards addressing Alzheimer’s disease funded by CIRM. One of those grantees, Frank LaFerla, is in this video about a discovery he made as part of the CIRM-funded research.

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