Where are the cures?

It seems like the stem cell news cycle alternates between stories of incremental hope (take the heart disease model for drug discovery out of Stanford today) and stories decrying the woeful lack of cures out of CIRM. I think the popular imagination went from the word “cure” when Proposition 71 passed in 2004 to an immediate need to see those cures by 2005. Or at least by 2011.

The very first stem cell-based “cure” came in 1968, when doctors at the University of Minnesota transplanted bone marrow from one person into a child with a genetic blood disease. Bone marrow contains the blood-forming stem cells that continuously rebuild the blood and immune system. Today, bone marrow or blood-forming stem cell transplants save lives daily, and are an active area of research by CIRM grantees working to develop new cures for HIV/AIDS, sickle cell anemia and other diseases.

Bone marrow and the related cord blood stem cells are the only stem cells that currently deserve the label “cure."

You can think of science like a giant hose with discoveries at the tap and cures coming out the nozzle. It’s a leaky hose, though, and ideas that look promising early on — and receive a great deal of press attention at the time — often leak out as they are disproven or shown to be ineffective. At CIRM, we fund the discovery end of the hose, constantly trying to generate good ideas that will one day make it out the other side. We fund the middle phases, where scientists figure out the best way of turning those early discoveries into cures (Here’s a video with Hans Keirstead explaining why that process takes so much time). And we fund the end everyone watches so closely — where the cures come out.

Bone marrow stem cells went in the discovery end of that hose decades ago, starting with research in the 1950s, and new therapies are still pouring out, including the recent Berlin patient who was effectively cured of HIV infection.

Various types of adult stem cell discoveries went into that hose starting in the 1990s as new tissue-specific stem cells such as those in the brain, fat, placenta and skin were discovered. Clinical trials involving those cells are still underway, which means that despite exciting news stories of mid-hose success the cells have yet to make it out the cures end of the nozzle. Many trials look promising, but until the cells are shown to be safe and effective in large controlled trials, they aren’t yet cures. CIRM funds a lot of adult stem cell research (here’s a list of those awards, many of which involve complex manipulations rather than the simple cell transplants of earlier work) and we’re excited about seeing some of the early discoveries start making it through clinical trials.

So, where are the embryonic stem cell cures? Well, they went into the discovery end of the hose in 1998 and we already have three clinical trials underway based on those cells. CIRM began funding stem cell research eight years later in 2006 and some of our grantees expect to be in clinical trials in the next few years. It’s true that they have yet to come gushing out the cures end of the nozzle, but it’s exciting to know that because of CIRM discoveries are at least in the the hose, making their way toward the end we're all watching so eagerly.

- 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.

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.

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.

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.