Bakersfield residents learn about stem cell progress in aging, macular degeneration

This weekend CIRM hosted an educational event in Bakersfield to update people on the progress being made by CIRM grantees. The event featured a keynote address by board chair Jonathan Thomas plus talks by grantees working on age-related diseases including blindness.

Although CIRM holds board meetings throughout California, this is the first time people in Bakersfield have had a chance to hear directly from CIRM. If media attention in advance of the meeting is anything to judge by, the local community was excited about hosting us. The local radio station KERN spoke with CIRM patient advocate coordinator Chris Stiehl, who helped organize the event. You can listen to that interview here.

Among other things, Stiehl discussed the Geron spinal cord injury trial as one sign that the field of stem cell research is progressing.

"Geron Corporation is doing clinical trials with stem cells on people with spinal cord injuries. That's amazing. We never had anything for those people except wheelchairs and someday they may get out of their wheelchairs because of this."

The Bakerfield Californian also had a nice piece announcing the event.

As with all CIRM patient advocacy events, if you can't make the event you can follow the discussion on Twitter either by watching the stem cell conversation on #stemcells or by following the event's hash tag, which is listed on the agenda on the CIRM web site. There's another event coming up October 29 in Santa Rosa, which you can follow at #CIRMSantaRosa.

These types of public events featuring CIRM scientists and patient advocates are going to be ongoing throughout the state as a way of making sure the people of California get a chance to learn about progress being made by the institute.

You can get more information about all the awards CIRM has funded and which institutes have received funding on our website.

A.A.

More stem cell firsts -- spinal cord injury and blindness

Tuesday was a very proud day here at CIRM headquarters. We were able to announce the enrollment of the first patient in a clinical trial funded, in part, by the agency. It was also a bit of a somber day as Paul Knoepfler pointed out in his blog yesterday. It meant the patient had recently undergone a life-changing tragedy that landed them in need of the hope the follow-on trials to this safety study might provide.

This morning's news feed brought a similar double-edged milestone. Stem Cells Inc, the Newark California-based biotech firm, announced that the day before their research team had injected adult neural stem cells into a spinal cord injury patient for the first time. The stem cells were administered at Balgrist University Hospital of the University of Zurich to a 23-year old German man who had suffered a spinal cord injury in an auto accident in April and was completely paralyzed below the waist.

A press release from the company posted on Yahoo has a quote from the patient that vividly points out the double-edged nature of this milestone to him:

"This terrible injury crossed out almost all my life plans, and has led me to an unexpected path. Participating in this clinical trial not only gives me a sense of hope, but it also helps move this important research forward."

There was another strong linkage between these two milestones. One of the lead surgeons at the Zurich hospital was Raphael Guzman who has a visiting appointment there and is on faculty at Stanford, where he is a colleague of Gary Steinberg who transplanted the cells in the CIRM-funded trial at Santa Clara Valley Medical Center.

Today's news feed brought a third milestone to our field. Advanced Cell Technology (ACT) announced that they had been given approval to begin the first clinical trial of cells derived from embryonic stem cells in Europe. They will be testing cells for a form blindness that strikes children called Stargardt's disease. Clearance to begin the trial came from the United Kingdom Medicines and Healthcare Products Regulatory Agency.

ACT launched a similar trial in the US in November 2010 and a second trial in January, this one for macular degeneration, the leading cause of blindness in the elderly. This summer the company announced the first patients were enrolled in each trial at UCLA in July.

Robert Lanza, chief scientific officer at ACT told a news organization in the UK in this morning's coverage:

"We're very pleased with the results so far. We're in the process of scheduling the next two patients for each of the two (US) trials."

We are keeping our fingers crossed that this early track record for safety holds.

DG

Three embryonic stem cell trials and counting

We’re back after a vacation filled with news about the second ACT embryonic stem cell trial getting FDA approval earlier this week. This one is for macular degeneration. Their first trial, approved by the FDA on November 22, was for Stargardt’s macular degeneration. That brings the total to three trials testing therapies based on embryonic stem cells.

For anyone who missed the ACT announcement in the midst of New Year’s excitement, here’s a good story from the MIT Technology Review.

It’s easy to get excited about this progress, and about the additional embryonic and adult stem cell trials I hope to see approved and started in the next year. Whatever the stem cell type, progress toward new therapies is something to celebrate. At the same time I do worry about the level of hope being placed on these first three trials. More early stage trials fail than succeed, and it is likely that at least one of these early embryonic stem cell trials will fail too. That’s the whole point of testing therapies in humans — no matter how effective a therapy might have been in mice or other animals, we humans respond differently and you just never know what to expect.

The Technology Review story had this to say about the many unknowns of the ACT trial:

A number of questions remain to be answered, including how well the cells will survive in a diseased eye. Increasing evidence suggests that macular degeneration is in part an immune defect, and some people with the disease have signs of inflammation in the retina, which may it more difficult for the implanted cells to take root. "That's something animal models haven't been able to look at carefully," says Reh.

It's also not yet clear whether, if the cells do survive, they will delay or prevent further vision loss, or actually improve vision. Transplants of retinal pigment epithelium cannot replace lost photoreceptors, but they may help damaged photoreceptors function better and in turn enhance vision.

I should add that the story had a lot to say about why the trial might succeed, too. 

I’m optimistic that some of these early stem cell trials will go on to be successful, and that some of the work CIRM has already funded will be making it’s way to trials shortly. I also hope people remember that when some of these trials aren’t successful the first time it doesn’t invalidate stem cell therapies. It just means stem cells are as difficult to bring to the clinic as vaccines or cancer chemotherapeutics or any of the many other therapies that now save lives every day.

- A.A.

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:



A.A.

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:




A.A.

Full Vision Cure? Full Stem Cell Research Required

By Don C. Reed

The world is delighted that patients with injured eyes in Italy regained their sight, thanks to the use of stem cells transplanted from their own good eyes. This is a wonderful victory for Dr. Grazziella Pellegrini, the University of Modena, and everyone involved. They are doubly to be congratulated because they are working with one hand tied behind their backs. In Italy, it is illegal to fund embryonic stem cell research. So they did what they could with what was allowed.

To give sight to someone who has been blinded in one eye is wonderful indeed.

But to claim this success invalidates the need for embryonic cells, which some have done, would be wrong.

First, the improvement only works on injured eyes, not those damaged by disease or genetic problems. This disqualifies the overwhelming majority of blindness sufferers, such as people with macular degeneration or retinitis pigmentosa. Also, not every injury can be treated. Everything depends on the patient having enough good tissue from the eye to draw cells from. It would be useless to a person born blind.

It has also been reported that another scientist was not able to duplicate Dr. Pellegrini’s success. According to a story in Bloomberg News Dr. Ivan Schwab, an ophthalmology professor and stem cell researcher at UC Davis:

"…has treated patients in clinical trials with a procedure based on Pellegrini’s work. While his patients improved for a time, the benefits didn’t endure."

Adult stem cell work has been studied for more than half a century; it would be shocking indeed if there were no successes. This particular study began in 1998—the same year human embryonic stem cells were first isolated.

As the father of a paralyzed young man (Roman Reed, inspiration for a California law which has funded embryonic stem cell research) I follow the research closely. This fall, we hope, an embryonic stem cell treatment will go to human trials.

Adult stem cell research is a useful tool. But it is only one tool, not the toolbox.

Patient advocates, like the vast majority of scientists, support full stem cell research, not any single kind to the exclusion of all others.

Don C. Reed
Citizen-sponsor, Roman Reed Spinal Cord Injury Research Act
Stemcellbattles.wordpress.com

Multilayer retinina created from embryonic stem cells

More news from UC Irvine, this time relating to retinal diseases such as macular degeneration, retinitis pigmentosa, and Stargardt’s disease. A group led by Hans Keirstead of the Reeve-Irvine Research Center and the Sue & Bill Gross Stem Cell Research Center created an 8-layer retina from human embryonic stem cells.

In a press release, Keirstead said:

“What’s so exciting with our discovery is that creating transplantable retinas from stem cells could help millions of people, and we are well on the way.”

According to the release, more than 10 million Americans suffer from macular degeneration, the leading cause of blindness in people over 55. About 100,000 have retinitis pigmentosa, a progressive, genetic disorder that usually manifests in childhood.

Keirstead’s is one of several groups of CIRM-funded researchers trying to create functional retinas for transplantation. This video describes work by Mark Humayun at the University of Southern California.



You can see beautiful images of retinal tissue created from embryonic stem cells on the CIRM Flickr photostream.

A.A.

Visual Function Rescued in Rats Using Cells derived from iPS Cells

Induced pluripotent stem (iPS) cells have created excitement and head scratching ever since they were first created a little over two years ago. The excitement arises from their creation through reprogramming adult cells by manipulating their gene function, which does not require a human embryo and could potentially give a patient personalized replacement cells. But determining just how identical they are to embryonic stem cells in function has caused much consternation.

Now, a team at UC Santa Barbara and University College London has provided some pro and con information on the functionality question. Working in a rat model for age-related macular degeneration in which defects in retinal pigmented epithelial (RPE) cells lead to death of photoreceptors, they showed that RPE cells grown from iPS cells inserted into the retina prior to photoreceptor death were able to rescue the receptors and the rats retained vision.

A press release from UCSB quoted Sherry Hikita, an author on the paper saying:

“Although much work remains to be done, we believe our results underscore the potential for stem-cell based therapies in the treatment of age-related macular degeneration.”

However, the team also saw a difference between the iPS derived RPE cells and embryonic stem cell-derived RPE cells used in earlier experiments. The ESC-derived cells survived after transplant long-term, where as the iPS-derived RPE cells suffered rejection by the immune system.  This would not occur if the cells were derived from the patient receiving the therapy, but many leaders in the field have hoped that banks of iPS cells could be developed that would be less expensive than deriving new cells for each patient. Also, these banked cells could avoid transplanting cells with the same genetic mutation that caused the problem in the first place.

In the December 3 PLoS  ONE the authors speculate:

“The embryonic origin of hESC-derived RPE may reflect a more immune privileged cell type in comparison to iPS-RPE.”

To further complicate the equation, the rats in this model retained long-term visual function despite rejection of the transplanted cells suggesting the transplanted cells induced some sort of protective response for RPE cells in the surrounding tissue.

PLOS ONE, December 3, 2010

CIRM funding: David Buchholz (T3-00009)


DG