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

First patient enrolls in a clinical trial funded by CIRM

Today is a landmark day for CIRM: We announced that the first patient had been enrolled in a clinical trial based on stem cell agency funding. You can read our press release here.

The patient was part of Menlo Park-based Geron's phase I trial for spinal cord injury, which was awarded $25 million from CIRM in May. Stanford neurosurgeon Gary Steinberg, MD, PhD, implanted the cells Sept. 17 at Rehabilitation Trauma Center at Santa Clara Valley Medical Center.

Stanford had this to say about the trial:

Researchers at Geron collaborated with Hans Keirstead, PhD, and his laboratory team at UC-Irvine to develop a way to coax human embryonic stem cells to become a mixture of cells that include oligodendrocyte precursors. Oligodendrocytes are cells in the brain and the central nervous system that wrap nerve cells with an insulating material called myelin. This myelin sheath is necessary for the transmission of the electric signals along the spinal cord that trigger muscles to move, and relay our sense of touch and temperature. Damage to this sheath caused by trauma is a common cause of paralysis.

To be eligible for the trial, patients must have recent (within 14 days of injury) non-penetrating damage to a specific region of their thoracic spine — an area roughly from the top of the shoulder blades to the bottom of the rib cage. The damage must cause complete paraplegia, meaning that they have normal sensation or movement to the level of the hands, but not from the trunk to the toes.

During the procedure, Steinberg applied about 2 million of the special cells, called GRNOPC1, directly into the injured area of the patient’s spinal cord.

“We are quite pleased that the surgery was completed successfully and the patient is doing well,” said Steinberg.

When the CIRM governing board voted to fund the Geron trial, spinal cord injury advocate Roman Reed wrote a guest blog entry in which he said:

In a truly historic partnership for stem cell research and cure, state funding from what has been called “Roman's Law” gave Hans Keirstead the seed money to achieve empirical evidence and proof of principle. Hans then sold his pioneering technique to Geron, and advanced biotechnology farther by founding California Stem Cell with the proceeds.

With admirable courage and determination, Geron pushed this science all the way to FDA approval to become the world's first embryonic stem cell derived human clinical trial.

Now our beloved state agency, the California Institute for Regenerative Medicine will provide funding to bring about a full and complete Human Clinical Trial!!

The Keirstead/Geron/CIRM Trials advances the entire field of stem cell research.

Today's announcement marks a milestone that is a critical step toward making safe and effective stem cell-based therapies available to patients.

A.A.

Guest blogger Roman Reed: spinal cord injury stem cell trials get $25 million boost from CIRM

From the editor: Yesterday the CIRM governing board approved a $25 million loan to help fund a trial testing the use of an embryonic stem cell-derived therapy for spinal cord injury. Here's our press release. Our guest blogger Roman Reed was injured in a football accident and has since fought tirelessly for spinal cord injury research.

Yesterday's announcement that CIRM will help fund the Geron spinal cord injury Human Trials ensures that paralysis cure will have it's day!

It was my honor to be the inspiration of the Roman Reed Spinal Cord Injury Research Act in 1999, which provided the original funding for Hans Keirstead's research which is being tested in these trials, the first in the world.

However, the expense of the trials might conceivably have exhausted Geron's financial resources, narrowing the scope of the trials. This would have been devastating, not only to our hopes for paralysis cure but also for the entire field. The world is watching. Had the trials been too limited for lack of funding, it might have cast a shadow of doubt on its outcome-- instead, the trials go forward, strongly.

Geron's nine year struggle to build a mountain of preliminary data (so the FDA could approve the human trials) was an heroic effort, on which so much depended. With the leadership of Geron, the courageous biomed company came through for California and our country, and the world-- and so did the California stem cell program.

When the oversight committee announced its decision yesterday, it authorized a $25 million dollar loan to Geron to assist in the clinical trials. This was a careful loan, milestone driven, with each installment given only on the successful completion of predetermined goals.

I join the patient advocate community across the globe in expressing absolute full support of CIRM's descision to provide funding for America's first hESC derived Human Clinical Trials.

As a Patient and Patient advocate, I am overjoyed that Prop.71 took a stand for the Geron trials, the most important experiment in the world for the fields of spinal cord injury, neuro-regenerative medicine and stem cell research.

Truly, the Geron Trials are setting the pace of spinal cord injury. Paralysis affects 650,000 Californians and 1.9 million Americans, with an additional 5.6 million Americans who suffer from all forms of paralysis. (Here's information about CIRM's funding for spinal cord injury stem cell research.)

This epic step was accomplished through partnership and collaboration through a new age continum of support beginning with State funding from Roman Reed Spinal Cord Injury Research Act, Education at the University of California, Irvine, private industry support from Geron and voter-approved CIRM/State funds.

In a truly historic partnership for stem cell research and cure, state funding from what has been called “Roman's Law” gave Hans Keirstead the seed money to achieve empirical evidence and proof of principle. Hans then sold his pioneering technique to Geron, and advanced biotechnology farther by founding California Stem Cell with the proceeds.

With admirable courage and determination, Geron pushed this science all the way to FDA approval to become the world's first embryonic stem cell derived human clinical trial.

Now our beloved state agency, the California Institute for Regenerative Medicine will provide funding to bring about a full and complete Human Clinical Trial!!

The Keirstead/Geron/CIRM Trials advances the entire field of stem cell research.

Today's vote of support is a truly historic milestone in medicine.

Ladies and Gentlemen welcome to the beginning of personalized stem cell medicine and cure!

Thank you Prop.71 for Taking A Stand-- So One Day-Everybody Can!

Here's Roman Reed discussing stem cell-based therapies for spinal cord injury:

First patient from Geron spinal cord injury trial speaks up

A story by Rob Stein at the Washington Post is reporting that the first patient to participate in Geron's groundbreaking embryonic stem cell-based trial for spinal cord injury has come forward.

This is both exciting news and no news. It's exciting because scientists and people living with spinal cord injury and their families are all watching this trial closely. Any news is of interest. However, at this point it's too soon to know if the cells have been effective.

For those who haven't been following this story, Geron is conducting a trial in which they inject primitive neural cells derived from embryonic stem cells into the region surrounding a recent spinal cord injury. In work with rodents conducted by CIRM grantee Hans Keirstead at the University of California, Irvine, the cells were able to restore movement to the hind limbs after an injury. (As an aside, that earliest work was conducted through funds from the Roman Reed Spinal Cord Injury Research Act, which is currently being debated by the state.)

The first patient was Timothy J. Atchison of Chatom, Ala. According to the Washington Post:

Atchison, known as T.J. to his family and friends, was a student at the University of South Alabama College of Nursing when his car crashed on Sept. 25, which, Atchison noted, was the birthday of Christopher Reeve, the actor who suffered a devastating spinal cord injury.

After undergoing emergency treatment at a regional medical center, Atchison was transferred to the Shepherd Center in Atlanta, which specializes in spinal cord injuries, for rehabilitation. It was there that he agreed to let doctors inject him with the drug — more than 2 million cells made from stem cells into his spine, he said.

Like all initial trials in the U.S., this one is primarily testing whether the cells are safe, but of course it is also being closely watched for signs that the cells were effective (read more from the NIH about phases of a clinical trial). It's too soon for scientists to know whether the injected cells are able to help repair damage after spinal cord injury such as the one Atchison suffered after his car crashed.

Geron intends to test the cells on 10 people at seven sites around the country, of which Stanford University recently announced it was one. The Washington Post describes the procedure:

Surgeons planned to use specially designed equipment to infuse into the first patient’s spine about 2 million “oligodendrocyte progenitor” cells, which Geron scientists had created in the laboratory from embryonic stem cells obtained from days-old embryos left over from fertility treatments. The hope is that the cells will form a restorative sheath around the damaged spinal cord. In tests in hundreds of rats, partially paralyzed animals regained the ability to move, according to Geron.

The Geron trial isn't the only approach to using stem cells to treat spinal cord injury, though it is the first to clinical trial. Here's a list of CIRM grantees working on other approaches, including some using adult, embryonic or reprogrammed iPS cells.

A.A.

A second stem cell trial for spinal cord injury

We've posted quite a bit about the Geron trial testing an embryonic stem cell-derived therapy for spinal cord injury. Now Palo Alto-based StemCells Inc has started a trial in Switzerland testing a tissue-specific stem cell therapy. The company announced that they'll be enrolling 12 people who have no feeling below their injury in this initial safety trial. Unlike the Geron trial, which is specifically enrolling people with recent injuries, StemCells Inc is testing their product in people whose injuries are three to twelve months old.

A significant difference between these two trials is the type of cell being tested. (You can read more about different types of stem cells in our Stem Cell Basics.) The Geron trial uses embryonic stem cells that have been grown in large quantities then matured into a type of neuronal precursor cells. In rodents, those cells are able to restore function after a recent spinal cord injury. The Geron trials will show whether those cells are also effective in people.

By contrast, the StemCells Inc trial uses cells that are already committed to becoming a type of neuronal cell. These neuronal stem cells can repair spinal cord injuries in rodents. Like the Geron trial, StemCells Inc is first testing these cells in a small number of people to ensure that they are safe.

It's exciting to see several different approaches being tested. When I think about these early stem cell trials I often reflect on the earliest cancer trials. I don't know very much about the first chemotherapy for lymphoma, but I'm grateful to the scientists who kept trying new approaches and improving on early successes because they're the reason my mother has been cancer-free for the past 10 years.

Whether or not these first trials are successful (and honestly, more early trials fail than succeed) we are witnessing the start of what I hope will one day be a cure for all those people living with spinal cord injuries. That cure might involve embryonic stem cells, neuronal stem cells, drugs tested on stem cells in the lab, or a combination of those approaches depending on the type of injury. CIRM is funding all of those stem cell approaches in the hopes finding the quickest path to a cure.

A.A.

Clinical Trial of Hope at Stanford -- guest blogger Roman Reed

Under the direction of Dr. Gary Steinberg, an advance long considered impossible is moving forward today: Stanford announced yesterday that it will participate in Geron's human clinical safety trials for a novel treatment for spinal cord injury. These are safety trials to be sure and not efficacy trials, more tests will need to be run, but this is already farther along than ever before.

To understand what this means to me, jump back in time…

Eight years ago, I held in my hand a paralyzed rat.

As I sat there in a wheelchair paralyzed from a spinal cord injury, holding this rat in wonderment, awe and jealousy, my mind barely comprehended that this rat was actually moving. His formerly paralyzed legs pushed strongly against my hands, trying to get away from my grasp. (A video of a rat from that test is available here.) His coat full and healthy, meaning he had no pain. This rat was the tangible realization of a seemingly impossible dream: to cure paralysis.

This was the pioneer rat of what would become the world’s first human embryonic stem cell clinical trials: the “Geron Trials”.

That rat walked because of Dr. Hans Keirstead at the University of California, Irvine Reeve-Irvine Research Center, whose brilliance is matched only by his courage and determination. Nearly everyone denied him funding initially, because his experiment was ‘too far reaching”. But he would not quit.

This rat was also walking again, because California’s Roman Reed Spinal Cord Injury Research Act of 1999 provided Keirstead the initial funding for this Pioneering Research! (CIRM has since funded Keirstead's follow-up research with a Comprehensive award.)

The first human clinical trials for hESCR treatment were accomplished because of Geron Corp. Geron is literally footing the bill: risking their financial backbone to advance the field. It is to be hoped they will be richly rewarded for such fiscal courage.

These trials of hope through stem cells are being overseen by Stanford’s brilliant Dr. Gary Steinberg and Dr. Steve McKenna of San Jose Valley Medical Center.

Stanford is committed to the cause of cure; and there too, I can speak from personal experience—because Dr. Steinberg is the founder and director of the Stanford Partnership for Spinal Cord Injury and Repair.

One day, I hope to fulfill the late great Christopher “Superman” Reeve’s prediction, that:

“One day, Roman and I will stand up from our wheelchairs, and walk away from them forever.”

Cure did not come in time for our great champion, but I believe he is smiling down on us this day, as Stanford, California, and the world take one leap toward the fulfillment of his dream.

Be mindful, this is just the beginning…



- Roman Reed is the namesake of the Roman Reed Spinal Cord Injury Research Act passed in California. As a result, more than $12.5 million in state funds has been awarded to scientists conducting research in spinal cord regeneration. An additional $50 million has been leveraged from outside sources.

Here is additional information about CIRM's spinal cord injury funding.

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.

A salute to caregivers from Leeza Gibbons

At CIRM we want nothing more than to find cures for the diseases that afflict people around the world. Until that day comes, many of the diseases we hope to cure — Alzheimer’s disease, Parkinson’s disease, spinal cord injury, ALS, to name a few — place an incredible burden on the caregivers in addition to the patients themselves.

Caregivers have no greater advocate than Leeza Gibbons, who also serves on the CIRM governing board. Her online caregiver support network, Leeza’s Place, is celebrating National Family Caregiver Month with events throughout the country to both support and educate caregivers. A list of those events is available here.

On her blog, Leeza wrote:

At Leeza’s Place, we know the job of being a caregiver is both frustrating and fantastic; isolating and invigorating; a blessing and a burden. Those husbands and wives, daughters, sons and friends who care for someone they love often find they are stronger than they ever imagined they could be.

As we celebrate those courageous spirits, we offer respect and gratitude to all who are on the front lines of humanity. A month recognizing caregivers is just a starting point for us to create more national awareness, better support, respite and care. At Leeza’s Place, this month (and every month) we offer hugs of support, approval and a blanket of love!

To hear more about Leeza’s Place and Leeza’s caregiving mantra of “Take Your Oxygen First” visit their online media page here.

Here is Dan Desmond, who has ALS, paying a touching tribute to his wife and caregiver, Gloria Desmond.



A.A.

Geron trial -- baby steps toward a cure

Today Geron announced that the first patient had been treated in their groundbreaking trial based on human embryonic stem cells.

At first blush: Woo hoo!! This is the first test of technology that holds hope for millions of people living with spinal cord injury and other diseases.

But it’s important to remember that this first trial is a very, very early step. Any potential therapy goes through three rounds of human trials. The first, phase I, trial is intended only to verify that the potential therapy is safe. This trial can establish dosing and begin to monitor side effects of the drug or treatment. In some cases a phase I trial will also begin to reveal whether the drug or therapy has signs of effectiveness, but that’s not the primary role of the trial.

After the small phase I trial comes a slightly larger phase II trial. It confirms safety and also begins to look directly at whether the drug or therapy is effective.

It isn’t until some years later that a large phase III trial confirms whether the drug or therapy is effective compared to standard therapy.

Many potential therapies fail after the phase I trial, even after years of positive results in animals. Humans aren’t mice (or other laboratory animals) and scientists can’t ever know what side effects will turn up in their human patients.

That’s why it is important to temper that initial “woo hoo” with a bit of patience. This could be one of those trials that fails phase I. Or phase II. Or phase III. But as many years of biomedical research have shown, for every failed trial there are also a number of successful trials. Whatever the results of this first phase I trial, it’s the beginning of a new era that will one day result in the first successful therapy based on human embryonic stem cells. That day will have scientists and patients alike whooping for joy.

Here's patient advocate Roman Reed talking about what a stem cell therapy for spinal cord injury means to him:

Running, cycling and swimming for a cure

Any excuse to link stem cell research and a favorite activity...

In the top 10 list of our most popular entries, spinal cord injury ranked among the topics of most interest to readers. And for good reason. It's the first condition to be approved for an embryonic stem cell trial. It's also a terrible condition in dire need of a therapy.

Those readers interested in helping find a cure for spinal cord injury might want to check out the Team Reeve Marathon season. Short of toiling in the lab, this a great way to move the research forward. The Reeve Foundation will help train runners in return for their fund-raising efforts.

If running for a cure sounds appealing but your heart lies with an ailment other than spinal cord injury, you can check out your favorite disease charity. Many raise money by training volunteers for marathons, triathlons, cycling events and hikes.

The Sanford-Burnham Medical Research Institute also recently posted information about Team Sanford-Burnham in which fund-raisers run with the scientists whose work they are supporting.

As runner Judy Wade, a Team Stanford-Burnham enthusiast, says about marathons she's run:

"You have to remind yourself why you’re doing this, the cause. You feel really good about yourself when you’re finished.”

(She's right!)

While out there raising funds you can also raise awareness of stem cell research. Here are some answers to the most common misconceptions about stem cell research.

A.A.

Update on stem cell treatments for spinal cord injury

A nod to Paul Knoepfler at UC Davis, who has posted a blog entry about the Geron trial for spinal cord injury. It provides a nice summary of the science behind the trial, and a reminder of why patients might be hard to recruit. He refers to Michael Martinez, a jockey who recently sustained a severe spinal cord injury, and who was rejected for participation in Geron’s trial developed from human embryonic stem cells. As Knoepfler points out:

An important element of this treatment, as highlighted by the recent case with Martinez, is that the injury has to be of a certain kind to be treatable using Geron's approach. If too severe, the animal models would suggest the treatment won't help. In addition, the treatment must be given with 1-2 weeks of the injury.

We recently released a video about stem cell therapies for spinal cord injury, featuring CIRM board member Oswald Steward who directs the Reeve-Irvine Research Center at UC Irvine. CIRM funds several spinal cord injury research projects at that center, including some with Hans Keirstead who first developed the therapy being tested by Geron.

While talking with Dr. Steward for that video he discussed hopes for a therapy that would be effective after that first 1-2 week window. His lab recently showed that in rodents, neurons could be nudged to regrow over the site of an older injury (here's the UCI press release). Another group at UC Irvine found that human neural stem cells restored some mobility to mice that were in the chronic stages of spinal cord injury (here's our blog entry on that work).

You can learn more about CIRM work toward a stem cell based therapy for spinal cord injury on our Spinal Cord Injury Stem Cell Fact Sheet.

Neural stem cells help mice with chronic spinal cord injury walk again

Human neural stem cells transplanted
into mice grew into neural tissue
cells, such as oligodendrocytes.
Brian Cummings / UCI

A study published last week by CIRM grantees at UC Irvine gives a big ray of hope to people living with spinal cord injuries. Brian Cummings and Aileen Anderson showed that human neural stem cells could restore some mobility to mice with induced spinal cord injuries. According to a press release from UC Irvine:

The UCI study, led by Aileen Anderson and Brian Cummings of the Sue and Bill Gross Stem Cell Research Center, is significant because the therapy can restore mobility during the later chronic phase, the period after spinal cord injury in which inflammation has stabilized and recovery has reached a plateau. There are no drug treatments to help restore function in such cases.

Other stem cell strategies for treating spinal cord injury, including the trial by Menlo Park, CA-based Geron, focus on the period of time immediately following injury.

In this latest work, three months after the stem cell treatment the mice showed consistent improvements compared to untreated mice.

The release quotes Aileen Anderson as saying:

“This study builds on the extensive work we previously published in the acute phase of injury and offers additional hope to those who are paralyzed or have impaired motor function.”

This seems like a good time to quote Roman Reed, the namesake of the Roman Reed Spinal Cord Injury Research Act and founder of the Roman Reed Foundation: “Turning stem cells into cures.” This paper is one more step toward that goal that we all share.

PLoS ONE, August, 19, 2010
CIRM funding: Desiree Salazar (T1-00008)

A.A.

Geron to begin stem cell trial for spinal cord injury

Hans Keirstead, UC Irvine

The FDA has lifted a clinical hold that has been in place since 2008 on Menlo Park, CA-based Geron's proposed trial for spinal cord injury. The multi-center phase I trial will be the world's first trial of a therapy based on embryonic stem cells.

In a press release, the company's president and CEO, Thomas Okarma, said:

"Our goals for the application of GRNOPC1 in subacute spinal cord injury are unchanged - to achieve restoration of spinal cord function by the injection of hESC-derived oligodendrocyte progenitor cells directly into the lesion site of the patient's injured spinal cord."

Alan Trouson, CIRM President, said:

“This is an important milestone for the whole field to have an embryonic stem cell therapeutic in clinical trials. We are looking with hope and expectation that the transplant will be safe and effective.”

The trial is based on work by CIRM grantee Hans Keirstead at UC Irvine. Prior to CIRM funding, his team matured embryonic stem cells into a form of neuronal cell called oligodendrocytes. When injected into rats with spinal cord injury, those cells protected the remaining spinal cord neurons and allowed the rats to walk.

In their press release, Geron described the reasons for the clinical hold:

The clinical hold was placed following results from a single preclinical animal study in which Geron observed a higher frequency of small cysts within the injury site in the spinal cord of animals injected with GRNOPC1 than had previously been noted in numerous foregoing studies.

In follow up work, Geron was able to prove to the FDA the safety of their stem cell product. The work directly leading to this clinical trial took place prior to the passage of proposition 71 to create CIRM. CIRM has funded follow-up work by Keirstead and others to improve on this potential therapy and expand the application of these cells to other diseases.

Here is Hans Keirstead discussing the long path from basic research to this clinical trial:





A.A.