CIRM Innovation: The Patient Advocate Role — Guest blogger Jeff Sheehy

Duane Roth, my colleague on the CIRM governing board where he serves as one of the vice-chairs, has just published an article, with the title, “The Third Seat at the Table: An Insider’s Perspective on Patient Representatives,” in the Hasting’s Center Report. The Center, an independent, nonpartisan, and nonprofit bioethics research institute, publishes its report six times a year to “explore the ethical, legal, and social issues in medicine, health care, public health, and the life sciences.”

His article, along with one I published in Nature earlier this year (“Advocates deserve room at the decision-making table”) describe one of the critical innovations found in the governance of CIRM: formal, powerful roles for patient advocates.


I serve on the governing board as a patient advocate for HIV/AIDS, and in that role I along with the other patient advocate board members have been able to directly influence the direction of the agency. Our voice has helped shape decisions regarding CIRM policies and funding. As Roth writes, patient advocates can grasp some of the most complex and thorny policy and scientific issues and “tip the scales” in the direction of sound public policy that seeks prudently to accelerate progress towards cures.

In his essay, Roth describes the genesis of active and vocal patient power through the response to AIDS in the 1980s and 90s, “which galvanized patient communities to unprecedented levels of scientific and political involvement.” He also points out the current struggles between advocates and the FDA, where patients with multiple sclerosis and prostate cancer have been frustrated by the agency’s decisions.

Roth forcefully argues for incorporating a formal role for “patient mediators” into the FDA’s product approval processes. “The costs would be negligible, and the payoffs in therapeutic efficiency, and procedural efficiency, and public confidence could be enormous.”

In my Nature article, I link the successful passage of Proposition 71 establishing CIRM to the unprecedented efforts of patient advocates around California and argue that scientists and policymakers have an obligation to include in the decision-making processes those who make their work possible.

As pluripotent (embryonic or iPS) cell approaches enter clinical space, formal inclusion of patient advocates into decision making roles along the lines suggested by Roth is absolutely essential if society is going to judiciously accept the inevitable failures that accompany most clinical research. Cell therapy has the potential to transform medicine, but the risks are as great as the potential.

In HIV/AIDS, we have seen risk mitigated by the unwavering willingness of an active patient and stakeholder community to tolerate failure. The patient communities seeking relief and cures through cell therapy are just as capable of evaluating and accepting risks and failures.

I would argue that Roth’s article with its recommendations is not only timely, but also urgent, and I hope that it inspires a dialogue leading to near term conclusive action to bring patient advocates into the decision-making process regarding new therapies.

- Jeff Sheehy is is director for communications at the AIDS Research Institute at UCSF, and a member of the CIRM governing board.

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.

CIRM gets with times, goes electronic

The end result of stem cell research — the cures, that is — would never come to be if it weren’t for all the people working behind the scenes to support the science and the grant-making. In this post I want to acknowledge a big step CIRM recently took in making the administration that much easier for our grantees and for us.

Once upon a time, a scientist who wanted funding from CIRM filled out a much-despised, convoluted, intricate Acrobat form. They printed multiple copies, and trusted their luck to the postal system to get it to CIRM by the deadline. It worked, but it’s 2011 and we’re SO over paper.

As of our most recently posted RFA (Disease Team Therapy Development Awards) we’re all electronic. Grantees fill out an application online. If their application gets funded, the grantee can manage that grant online. Progress reports? Well, they still have to pull together the data, but it can be submitted online. Publications? Report them online. New applications? They go into your user account and you can manage all those grants from the same place. Time to submit a new form? No problem, CIRM makes sure there’s a notice in your account. Less time battling forms means more time doing research, which is good news for all people eager for new stem cell therapies.

I’m not a grantee, so these miracles are all a bit abstract. However, I do know people inside CIRM are looking forward to not taking angry calls from grantees who are frustrated with our forms. And they are looking forward to having that data automatically in our database rather than needing to import it from PDF.

The public will start seeing the benefit of these electronic developments over the next few months. Information that’s in our database can also be displayed on our website. I’m excited to start posting progress information and publications as part of our grant summaries. Stay tuned.

- A.A.

City of Hope performs 10,000th bone marrow transplant, works toward therapy for HIV/AIDS

Last week the City of Hope announced performing their 10,000th bone marrow transplant since 1976 when they were among the first centers to carry out the risky procedure. They said:

City of Hope performed its first successful bone marrow transplant in 1976 on a young college student from Indiana who was diagnosed with acute myeloid leukemia. His physician told him he should prepare himself for inevitable death. But his cousin, a physician in Los Angeles, knew that City of Hope was launching a bone marrow transplant program. The young student went to City of Hope to undergo a bone marrow transplant, and he has remained in remission for 35 years.

Bone marrow transplants are the original stem cell transplant because it’s the blood-forming stem cells in the bone marrow that are being transplanted from the donor and that rebuild the blood supply of the sick person. The procedure has dramatically increased survival rates for diseases such as leukemia, lymphoma and myeloma, and in one recent dramatic case also seems to have treated an AIDS patient.

This AIDS patient — widely known as the Berlin patient — received blood-forming stem cells from a person who was immune to HIV. Those cells rebuilt the patient’s blood system with cells that could resist the HIV virus. The announcement of that case was dramatic and exciting. However, there aren’t enough HIV-resistant people to provide transplants for all people infected with HIV. CIRM is funding two teams of researchers — including one at City of Hope — who are genetically engineering blood-forming stem cells to contain the mutation that seemingly cured the Berlin patient. A transplant with those cells could leave patients resistant to the infection and carry less risk because it’s their own cells being modified. We should know in a few years whether the FDA considers the research ready to test in humans.

What’s interesting is that the City of Hope announcement about their 10,000th bone marrow transplant is being hailed by some as a victory for adult stem cells. Blood-forming stem cells have by now cured countless people of blood diseases, but they can’t cure diseases of the nerves, liver, pancreas or any organ other than blood. Mesenchymal stem cells, also found in bone marrow, have been tested as therapies in a number of diseases, and they seem to have improved symptoms in some diseases, but they have not been shown to replace damaged tissue or cure the disease.

Scientists have found tissue-specific stem cells in many organs and one day they might be used to treat disease — and if they do there’s little doubt CIRM will have been involved in some way in that discovery. Some CIRM grantees are already working to develop new therapies with tissue-specific stem cells from brain. But until there’s a cure for every disease that has yet or could one day strike my loved ones, I think it’s too early to claim which stem cell type is best for all diseases.

This video about the City of Hope HIV/AIDS disease team features CIRM board member Jeff Sheehy:

- A.A.

Stem cells model heart disease, test drugs

Nature has a story that features a promising use for stem cells, and also provided a creative outlet for whoever is writing headlines over there: “Cells snag top modelling job”.

Nature isn’t covering America’s top model. They’re talking about modeling disease, in this case a heart condition called long QT syndrome. Both embryonic or iPS cells can be matured into any adult cell type. If those cells carry mutations that cause disease then they’ll mature into adult cell types that, in some cases, display that disease.

For something like long QT syndrome, in which the heart tissue has an altered beat, stem cells carrying a mutation that causes the condition provide the only way of testing drugs in a lab. The story mentions Mike Venuti, president of CIRM-funded biotech company iPerian:

His firm has made iPS cells from people with Alzheimer’s disease, Parkinson’s disease and type 2 diabetes and converted them into various cell types for drug screening. He expects that drugs identified using this method will reach clinical trial for conditions such as spinal muscular atrophy in the next few years.

CIRM funds work by Bruce Conklin at the Gladsone Institute of Cardiovascular Disease, who is taking cells from people with heart conditions, creating iPS cells, and using those cells to study the condition and test drugs. This video features Conklin discussing his cells’ top modeling work.

- A.A.

Embryonic stem cells provide limitless source of platelets

A story in yesterday’s L.A. Times highlights a point that I think often gets lost in the brouhaha over adult vs. embryonic stem cells. Adult stem cells are great, they really are. That’s why we fund a lot of work with blood, brain, fat and other tissue-specific stem cells (you can see a complete list of those awards here). But they don’t multiply in the lab. That’s why my husband spends two hours donating platelets every few weeks. He donates, hospitals use his platelets, and then he donates more.

Labs can’t multiply donated platelets in the lab, nor can they grow up large quantities of the blood-forming stem cells that produce platelets in the body. If they could, those blood-forming stem cells taken from bone marrow or cord blood could become an endless source of platelets and other mature blood cells.

A great thing about embryonic (or iPS) cells is that you can grow them indefinitely. And when you need more cells, you just take some of those so-called pluripotent cells, differentiate them into your cell type of choice, and voila… differentiated cells. As many as you need.

The L.A. Times story discusses recent work by a team of researchers including some from the company ACT published in the journal Cell Research. They were able to generate large of amounts of platelets from embryonic stem cells. According to the L.A. Times, the cells worked, too:

The researchers reported that the lab-grown platelets were “indistinguishable” from normal blood platelets — similar in shape and size — and that they behaved like the real thing, too, helping to form clots in lab dishes and in mice who had sustained injuries to blood vessels. The embryonic stem cell-derived platelets also helped retract clots, the team wrote, another key part of platelets’ role in healing wounds.

If this work is effective in humans it could end my husband’s two-hour down-time donating platelets every three weeks, which, truth be told, I think he might actually miss. But it could also mean an end to the chronic problem of platelet shortages in hospitals.

A.A.

Blood Stem Cell Finding Could Yield Practical Results for BMT

A finding by CIRM-funded researchers at the University of California Santa Cruz sounds pretty esoteric, but could be immensely practical for patients facing a grueling Bone Marrow Transplant (BMT).

Hematopoietic, or blood-forming, stem cells really have one preferred home. They tend to stick to their niche in the bone marrow, with relatively few circulating in the blood stream at any one time. That is why BMT has generally required anesthesia to go in and harvest bone marrow to get the stem cells buried within it. Lately, physicians have been trying to bypass this painful step by giving repeated injections of drugs over time to get the stem cells to leave the bone marrow and circulate in the blood stream where they can be harvested much more easily. But so far, this is still not very efficient and requires the multiple injections.

The UCSC team, lead by Camilla Forsberg, found that a rare molecule, Robo4, anchors the stem cells in the marrow. A drug that blocks Robo4 could be a safer and more effective way of getting stem cells out of the marrow and into the blood circulation where they could be harvested.

In a press release from UCSC Forsberg said:

“If we can get specific and efficient inhibition of Robo4, we might be able to mobilize the hematopoietic stem cells to the blood more efficiently. We’re already working on that in the second phase of the project.”

Another practical gain may come out of the teams work. Unlike most other types of stem cells, hematopoitic stem cells (HSCs) are very difficult to grow in the lab. They want that comfy home in the bone marrow. Knowing the role of Robo4 might let researchers fluff up the couch in those petri dishes and make the blood forming cells feel more at home. Much more could be learned about HSCs, much more quickly, if that became true.

CIRM Funding: Camilla Forsberg (RN1-00540-1)
Cell Stem Cell, January 2011

D.G.

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.