Faster, better, more efficient. Challenging? That too. An update on CIRM 2.0.

Changing direction is never easy. The greater the change the greater the likelihood you’ll have to make adjustments and do some fine-tuning along the way to make sure you get it right.

On January 1st of this year we made a big change, launching CIRM 2.0. Our President and CEO Dr. C. Randal Mills called it “a radical overhaul of the way the Agency does business.” This new approach puts the emphasis on patients, partnerships and speed and cuts down the time from application to funding of clinical-stage projects from around two years to just 120 days.

You can read more about 2.0 here.

So, several months into the program how are we doing?

Clinical stage of CIRM 2.0 has three programs

Clinical stage of CIRM 2.0 has three programs

Well, since January 1st we have had three application tracks under 2.0 that reflect our goal of accelerating therapies to patients with unmet medical needs. These focus on late stage work to either get a promising therapy into a clinical trial, to carry out a clinical trial, or to help a promising project move even faster.

Under those three programs we have had 12 applications for funding, for a total request of $111 million. With application deadlines the last business day of each month two of those were in January, two in February, three more in March and five in April.

As Dr. Mills told our governing Board when they met last week, that number is more than we were expecting:

 “When we started the program we calculated there’d be around one or two applications a month, not five. I don’t think having five applications a month is sustainable, but that’s probably just the backlog, the pent up demand for funding, working its way through the system. For now we can cope with that volume.”

Interestingly eight of those applications were for funding for clinical trials:

  • Two for Phase 1
  • One for Phase 2
  • Five for Phase 3

Last week our Board approved one of those Phase 3 trials (the last big hurdle to clear before the Food and Drug Administration will consider approving it for wider use), investing almost $18 million in NeoStem’s therapy for one of the deadliest forms of skin cancer, metastatic melanoma.

This is the first time we have ever funded a Phase 3 trial. So, quite a milestone for us. But it may well not be the last one. The Board also approved a project to conduct the late preclinical work needed to apply to conduct a trial in retinitis pigmentosa.

Dr. Mills said there are two clear patterns so far:

“We are getting a more mature portfolio of clinical stage programs for adjudication. We are also starting to see requests for accelerating activities, where we have made previous awards to researchers who now have identified new ways to accelerate that work and they are turning to us for help in doing that.”

Of the 12 applications received we have screened all of them within the 7-day target window to make sure they meet funding criteria. Some have been ruled out for not being within the scope of the award program. The accepted applications have all had budget reviews and been sent on for expert analysis within the slated time frames.

We had a couple of hiccups with our first review but that resulted from on-line technology and getting everyone comfortable with the new rules we were bringing in. The second review resulted in the first two awards by our Board last week, and the third review occurred yesterday.

“The bottom line is things are moving through and things are being weeded out. In March we had two clinical stage applications and one add-on funding application but that one add-on failed in screening. So, in general CIRM 2.0 is being well utilized. There’s no question we are significantly reducing application time from application to funding, attracting later stage applications. Clearly this has not been without its challenges but the team is doing a great job of managing everything.”

And remember this is only the first part of CIRM 2.0. We have two other programs, for Discovery or basic research and Translational research, that are being developed and we plan on rolling those out later this summer.

Stay tuned for more details on those programs.

Two for 2.0 and Two for us

It began as an ambitious idea; yesterday it became a reality when the CIRM Board approved two projects under CIRM 2.0, one of them a Phase 3 clinical trial for a deadly form of skin cancer.

Just to recap, CIRM 2.0 was introduced by Dr. C. Randal Mills when he took over as President and CEO of the stem cell agency last year. The idea is to speed up the way we work, to get money to the most promising therapies and the best science as quickly as possible. It puts added emphasis on speed, patients and partnerships.

Yesterday our Board approved the first two projects to come before them under this new way of working. One was for almost $18 million for NeoStem, which is planning a Phase 3 clinical trial for metastatic melanoma, a disease that last year alone claimed more than 10,000 lives in the U.S.

This will be the first Phase 3 trial we have funded so clearly it’s quite a milestone for us and for NeoStem. If it proves effective in this trial it could well be approved by the Food and Drug Administration (FDA) for use in melanoma patients. The therapy itself is unique in that it uses the patient’s own tumor cells to create a personalized therapy, one that is designed to engage the patient’s immune system and destroy the cancer.

The Board also approved almost $5 million for Cedars-Sinai in Los Angeles to do the late-stage research needed to apply to the FDA for approval for a clinical trial to treat retinitis pigmentosa (RP). RP is a nasty, degenerative condition that slowly destroys a patient’s vision. There is no cure and no effective therapy.

We are currently funding another clinical trial in this area. The two projects use different types of cells and propose different methods of reducing RP’s devastation. CIRM has a record of trying multiple routes to achieve success when dealing with unmet medical needs.

As Dr. Mills said in a news release, both the therapies approved for funding yesterday support our mission:

“CIRM 2.0 is designed to accelerate the development of treatments for people with unmet medical needs, and these two projects clearly fit that description. With the Board’s approval today we will now get this work up and running within the next 45 days. But that’s just the start. We are not just providing financial support, we are also partnering with these groups to provide expertise, guidance and other kinds of support that these teams need to help them be successful. That’s the promise of CIRM 2.0. Faster funding, better programs and a more comprehensive approach to supporting their progress.”

CIRM Chair Jonathan Thomas swearing in new Board members Adriana Padilla and Bob Price

CIRM Chair Jonathan Thomas swearing in new Board members Adriana Padilla and Bob Price

Two seemed to be the number of the day yesterday with the Board welcoming two new members.

Dr. Adriana Padilla is the new Patient Advocate Board member for type 2 Diabetes. She’s a family physician, a member of the University of California, San Francisco-Fresno medical faculty, and an award-winning researcher with expertise in diabetes and its impact on Latino families and the health system in California’s Central Valley. She is also active in the National Hispanic Medical Association (NHMA) and is also a member of the American Diabetes Association.

Dr. Padilla said she hopes her presence will help increase awareness among Latinos of the importance of the work the agency is doing:

“When I was asked about being on the Board I did some research to find out more and it was really touching to learn about some of the exciting work that has been done by the agency and the possibilities that can be done for patients, including those I serve, members of the Latino community.”

Dr. Bob Price is the Associate Vice Chancellor for Research and a Professor of Political Science at U.C. Berkeley. His academic and teaching interests include comparative politics, with a particular interest in the politics of South Africa. This is Dr. Price’s second time on the Board.  He previously served as the alternate to UC Berkeley Chancellor Robert Birgeneau.

Although he has only been off the Board for a little more than a year Dr. Price said he is aware of the big changes that have taken place in that time and is looking forward to being a part of the new CIRM 2.0.

Stem cells, Darth Vader and the high cost of hope and hype

Darth Vader: Photo by Stefano Buttafoco

Darth Vader: Photo by Stefano Buttafoco

It’s not very often that you get stories about stem cells that mention Darth Vader, Obi Wan Kenobi, the Pittsburgh Steelers and a Beverly Hills plastic surgeon, but those references all popped up in a recent flurry of articles that are shining – yet again – the light on many of the unproven, unregulated uses of stem cells to treat everything from arthritis to Parkinson’s disease.

Let’s start with an article by Associated Press (AP) writer Will Graves who digs into the use of stem cells in sports.  Graves does a good job of highlighting all the reasons why an athlete would try a stem cell therapy quoting Dr. Jim Bradley, a team physician with the Steelers:

“They want the cutting edge, anything that is cutting edge that can get their guys a couple more years in the league. If I was an agent, I’d want the same thing.”

But Graves also does a fine job of pointing out that these therapies are unproven, and that in many cases athletes go overseas to get them because those clinics do not have to meet the same strict regulations as clinics here in the US.

“Traveling to a place like the Caymans, that’s like saying ‘I’m going to Mexico to have an appendectomy to save $80,'” said Dr. Matthew Matava, head physician for the St. Louis Rams and the NHL’s St. Louis Blues. “It looks like it’s not very smart or you’re grasping at straws.”

He also quotes Dr. Freddie Fu, head physician for the University of Pittsburgh athletics program, saying there is far too much uncertainty to take risks. Fu says in many cases the people delivering the therapies don’t even know where these stem cells might go, or what they might do:

“You can have one cell be Obi Wan Kenobi, the other is Darth Vader. You’re not sure which way it’s going to go.”

Matthew Perrone starts his piece in the Huffington Post, with a paragraph that is both gripping and disgusting:

“The liquid is dark red, a mixture of fat and blood, and Dr. Mark Berman pumps it out of the patient’s backside. He treats it with a chemical, runs it through a processor — and injects it into the woman’s aching knees and elbows.”

Berman, the co-founder of the largest chain of stem cell clinics in the US, admits he doesn’t know what’s in the mixture he is injecting into patients. But he says it can help treat more than 30 different diseases and conditions from Lou Gehrig’s disease to lupus and even erectile dysfunction.

Perrone’s piece is a long, detailed and thoughtful look at the finances that drive this business and how many stem cell clinics charge as much as $9,000 for unproven therapies. He quotes UC Davis stem cell researcher – and CIRM grantee – Dr. Paul Knoepfler:

“It’s sort of this 21st century cutting-edge technology. But the way it’s being implemented at these clinics and how it’s regulated is more like the 19th century. It’s a Wild West.”

But the price tag at those US-based clinics is tiny compared to how much some people are paying at overseas facilities. Los Angeles Times reporter Alan Zarembo focuses on the case of William Rader and his company Stem Cell of America.

Rader, a psychiatrist, had his medical license revoked by the Medical Board of California citing negligence, false or misleading advertising and professional misconduct. The Board said: “His dishonesty permeates every aspect of his business and practices.”

Yet Rader continues to charge up to $30,000 for stem cell procedures at the clinic he runs in Mexico. He uses the same procedure for different conditions, offers no scientific evidence it works but claims he’s helped many people and even cured a patient of HIV/AIDS.

For patients battling life-threatening diseases and disorders it is easy to see why they would be willing to take a chance on a therapy, any therapy, that might save their life.

And that’s where the danger in all this lies. What might be seen by an athlete as something worth trying to see if it might help extend their career a year or two, for people at the other end of life this may be their last chance, and that vulnerability means they’ll pay whatever they have to, for something that may be of no benefit whatsoever.

Telling an athlete this might help them play longer is one thing. Playing on a patient’s life or death fears is entirely another.

For more information on how you can make an informed decision about whether a stem cell therapy is right for you, particularly one offered overseas, go to our page on stem cell tourism.

Taking a step back, to move forward

Progress doesn’t always come in straight lines. Particularly when you are a pioneer in a whole new field of medicine like stem cells where virtually everything you do is being done for the first time, and the therapies you are developing are going to be tested in people for the first time. That’s why everything you do has to be done with extra caution to make sure the best interests of the patients come first. Sometimes that means not rushing ahead, but pausing, while you decide what is the best approach.

SangamoThat’s what Sangamo have done in announcing they are delaying the start of their clinical trial in beta thalassemia – a trial we are funding.

They are taking what amounts to a “time-out” so that they can make a small change in direction, one they – and we – hope will ultimately prove most effective for patients.

Βeta thalassemia is a genetic disease that results in patients producing red blood cells with poorly functioning hemoglobin, the protein that carries oxygen to all our tissues. If not properly managed the condition can be fatal.

The approach Sangamo are taking to cure the problem involves using zinc finger nuclease (ZFN), a kind of molecular scissors, to genetically edit the patient’s own stem cells, correcting the problem and enabling them to produce healthy hemoglobin and healthy red blood cells.

But as they geared up for the clinical trial, one that was approved by the Food and Drug Administration (FDA), they did some preclinical testing and saw that an approach they were using on a similar disease – sickle cell disease (SCD) – appeared to be more efficient and effective at correcting the underlying genetic problem. Both used ZFN to edit the defective gene, but they both had slightly different targets on those genes. The one targeting SCD seemed to have some key advantages, so they have decided to switch to this approach for both conditions.

In a news release Edward Lanphier, Sangamo’s President and CEO, says it wasn’t an easy decision to make, but it is the right decision:

“While our joint decision will result in a delay in the initiation of the beta-thalassemia Phase 1 clinical trial, we believe that the efficiency of the consolidated development path and potential benefit to patients clearly support this decision.”

The next step is for Sangamo to go back to the FDA and file a new Investigational New Drug or IND application for this new approach to beta-thalassemia. They’re hopeful they’ll be able to get that approval, and move ahead with their clinical trial next year.

The good news is that thanks to our new way of funding under CIRM 2.0, Sangamo will have the opportunity to seek CIRM’s support for its work through both our preclinical program, as they make their changes, and then our clinical program if and when they get FDA approval to move ahead. This uninterrupted support is what CIRM 2.0 was set up to achieve, to move promising projects like this to patients as quickly as possible.

For the team at Sangamo it’s obviously disappointing to have to stop and change direction. It’s also disappointing for the patients hoping this would lead to a more effective therapy, even a cure.

But this is not a set back. Rather, it’s a step back. One that allows Sangamo to choose what they believe is a better option, one that will ultimately be much better for patients.

Stem cell stories that caught our eye: reversing aging, mature hearts, arthritic knees and tiny organs

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Young brain cells (top) show little of the molecule that impairs stem cell function (green) that is abundant in old cells (bottom).

Young brain cells (top) show little of the molecule that impairs stem cell function (green) that is abundant in old cells (bottom).

Making stem cells feels young again. Stem cells are supposed to rejuvenate our tissues, whether brain or muscle, and keep them functioning at their peak. But the aging process seems to poison the environment where stem cells reside and prevent them from getting the job done.

A CIRM-funded team at the University of California, Berkeley, has found a drug that can reverse the effect of aging and make the stem cells function better and in turn make tissues behave like younger versions of brain or muscle. Their previous work had shown that old tissues had much more of one growth factor, TGF-beta1, than young tissue. When the team, led by David Schaffer and Irina Conboy, blocked the activity of that growth factor with a cancer drug already in clinical trials they saw rejuvenated youthful tissue—in mice.

HealthCanal picked up the university’s press release, in which Schaffer described the broad effect of the treatment:

“We established that you can use a single small molecule to rescue essential function in not only aged brain tissue but aged muscle. That is good news, because if every tissue had a different molecular mechanism for aging, we wouldn’t be able to have a single intervention that rescues the function of multiple tissues.”

The team, however, noted that multiple molecular signals are in play in the aging stem cell’s environment and optimum intervention may require using more than one drug and getting the dosages just right. Conboy said that the task was to “recalibrate the environment to be youth-like.”

Maturing of the heart. Scientists can turn embryonic stem cells into most forms of adult tissue, but often those tissues don’t function like fully mature forms of the organ they are supposed to be. Now a consortium of researchers has identified a molecular switch that seems to be able to take stem cells and get them to form fully mature heart muscle.

In an interview with Genetic Engineering & Biotechnology News, senior author on the paper Hannele Ruohola-Baker of the University of Washington noted the breakthrough:

“Although we can now induce embryonic stem cells to become heart cells, getting them to mature to an adult-like state remains a significant challenge. We believe we’ve now found the master switch that drives the maturation process.”

The researchers found the molecular switch by studying many of the genetic switches called micro-RNAs in both young and old heart muscle cells. The one linked to helping stem cells mature interestingly is also involved in up-regulating metabolism and it makes sense that a supercharged metabolism would be valuable for fully functional heart muscle.

Some answers may be coming on stem cells and knees. While many clinics around the word offer to treat arthritic knees with stem cells taken from a patient’s own fat—often for large sums of money—very little data exist on the outcomes of those treatments. So, it was great to read this week that a European consortium is about to launch a large trial that should provide some quality data.

The ADIPOA-2 trial will enroll 150 patients in a randomized way so that the stem cell treatment can be compared to standard therapies, and the researchers will handle processing of the fat stem cells in a consistent way across clinics in four countries. It follows a phase 1 ADIPOA trial with 18 patients that showed promising results.

Frank Barry of the National University of Ireland Galway is coordinating the phase 2 trial and was quoted in the university’s press release picked up by HealthCanal:

“The results from ADIPOA’s first-in-man-trials were very encouraging and paved the way for another study to further test the safety and effectiveness on a wider scale. ADIPOA-2 is bringing together Europe’s leading scientific, clinical and technical expertise on this project.”

A lingering question remains about how long any benefit from the stem cell therapy will last. Some researchers have suggested that fat stem cells can only form soft cartilage like in your ear lobe and not the articular hard cartilage normally in your knee. So, it will take some years of follow-up to see if any new cartilage made by the stem cells can stand up to the beating of a good tennis match or hike up a mountain.

CIRM funds a research team at the University of Calirfornia, San Diego, that believe they have found a way to get embryonic stem cells, which are more versatile than fat stem cells, to form the hard articular cartilage.

Great hope in tiny little organs. For the past couple years one of the hottest areas of stem cell science has been growing stem cells in 3-D cultures in the lab and getting them to self organize into multi-tissue layers that mimic some function of one of our vital organs. It has been done for the eye, lung, liver, kidney and brain, but the first was the intestine, and the researcher behind the advance, Hans Clevers, dubbed them “organoids.”

The journal Nature just published a good Q&A interview with Clevers who works at the Hubrecht Institute Utrecht, the Netherlands. In it he describes how organoids will be a useful tool for drug screening and how his team is working on ways that organoids made from a patient’s own cells could be tested in the lab for sensitivity to specific cancer therapies.

How stimulating! A new way to repair broken bones

For those of us who live in earthquake country the recent devastating quakes in Nepal are a reminder, as if we needed one, of the danger and damage these temblors can cause. Many of those injured in the quake suffered severe bone injuries – broken legs, crushed limbs etc. Repairing those injuries is going to take time and expert medical care. But now a new discovery is opening up the possibility of repairing injuries like this, even regenerating the broken bones, in a more efficient and effective way.

shutterstock_18578173A study published in Scientific Reports  shows that it is possible to regrow bone tissue using protein signals from stem cells. Even more importantly is that this new bone tissue seems to be just as effective, in terms of the quantity and quality of the bone created, as the current methods.

In a news release senior author Todd McDevitt, Ph.D., said this shows we might not even need whole stem cells to regenerate damaged tissue:

“This proof-of-principle work establishes a novel bone formation therapy that exploits the regenerative potential of stem cells. With this technique we can produce new tissue that is completely stem cell-derived and that performs similarly with the gold standard in the field.”

McDevitt – who is now at the Gladstone Institutes thanks to a research leadership award from CIRM  – extracted the proteins that stem cells produce to help regenerate damaged tissues. They then isolated the particular factors they needed to help regenerate bones, in this case bone morphogenetic protein or BMP. That BMP was then transplanted into mice to stimulate bone growth. And it worked.

While this compares favorably to current methods of regenerating or repairing damaged bones it has a few advantages. Current methods rely on getting bones from cadavers and grinding them up to get the growth factors needed to stimulate bone growth. But bones from cadavers can often be in short supply and the quality is highly variable.

As McDevitt says:

“These limitations motivate the need for more consistent and reproducible source material for tissue regeneration. As a renewable resource that is both scalable and consistent in manufacturing, pluripotent stem cells are an ideal solution.”

He says the next step is to build on this research, and try to find ways to make this method even more efficient. If he succeeds he says it could open up new ways of treating devastating injuries such as those sustained by soldiers in battle, or by earthquake victims.

Using stem cells to mend a broken heart and winning $6,000 to boot

It’s no secret that the members of the CIRM blog team are all big fans of scientists who are good public communicators. We feel that the more scientists talk about their research, the better the public will understand the importance of science and it’s ability to help them or someone they love.

Grad Slam winner, Ashley Fong from UC Irvine

Grad Slam winner, Ashley Fong from UC Irvine

So on Monday when University of California, Irvine researcher Ashley Fong won the $6,000 top prize in the Grad Slam competition for the terrific explanation of her work in using stem cells to treat heart disease, it was doubly gratifying. You see, not only is Ashley a great communicator, but she’s also someone we have helped support in her career.

The Grad Slam is an “elevator pitch” competition sponsored by the University of California Office of the President. Ten graduate students from across the UC system were given three minutes to explain their work to a live audience, using everyday language and avoiding jargon or technical lingo.

All the students were good. Ashley was great. Want proof? Here you go (Ashley comes on at 39.20 into the video.)

She says she discovered her passion for stem cell research thanks to a CIRM-funded summer undergraduate internship. Now she is working in the lab of Chris Hughes at UCI.

In a UCI News story about the competition Frances Leslie, dean of the Graduate Division who hosted the campus-level competition in April, said:

“It’s important for graduate students to explain their research to the general public in ways that are easy to understand. And it’s also critical for the taxpayers of California to see the benefits of their support of graduate education.”

We couldn’t have put it any better.

Stem cell stories that caught our eye: spina bifida, review of heart clinical trials, tracking cells and cell switches

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cells boost fetal surgery for spina bifida. Fetal surgery to correct the spinal defect that causes spina bifida has revolutionized treatment for the debilitating birth defect in the past few years. But for one of the researchers who pioneered the surgery it was only a half fulfilled hope. While the surgery let most of the treated kids grow up without cognitive deficits it did not improve their ability to walk.

spina_bifida-webNow that researcher, Diana Farmer at the University of California, Davis, has found a way to complete the job. Though it has only been used in an animal model so far, she found that when you engineer a stem cell patch that you insert into the gap before you push the protruding spinal cord back in its place during surgery, the animals are able to walk within a few hours of birth.

Specifically, she used a type of stem cell found in the placenta that has been shown to protect nerves. She incased those cells in a gel and placed them on a scaffold to hold them in place after transplant. All six lambs that had surgery plus the cell transplant walked. None of the ones who just had surgery did.

“Fetal surgery provided hope that most children with spina bifida would be able to live without (brain) shunts,” Farmer said. “Now, we need to complete that process and find out if they can also live without wheelchairs.”

CIRM awarded Farmer’s team funds in March to carry this work forward and prepare it for a possible clinical trial. The animal study appeared in Stem Cells Translational Medicine this week and the university’s press release was picked up by HealthCanal.

Thorough, digestible review of heart trials. Kerry Grens, writing in The Scientist, has produced the most complete and understandable review of the clinical trials using stem cells to treat heart disease that I have read. More important she provides significant detail about the three large Phase 3 trials that are ongoing that could provide make-or-break outcomes for using bone marrow stem cells for patients developing heart failure.

The bulk of the piece focuses on research using various types of mesenchymal stem cells found in bone marrow. All three of the late stage clinical trials use those cells, two use cells from the patient’s own marrow and one uses cells from donors. Grens uses a broad spectrum of the research community describe what we currently know about how those cells may work and more importantly, what we don’t know. The experts provide a good point-counter-point on why there are so many clinical trials when we don’t really know those stem cells’ “method of action,” why they might make someone’s heart stronger.

However she leads and ends with work CIRM funds at Cedars-Sinai and Capricor Therapeutics in Los Angeles. That work uses cells derived from the heart called cardiosphere-derived cells. Early trials suggested these cells might be better at reducing scar tissue and triggering regrowth of heart muscle. Those cells are currently being tested in a Phase 2 study to try to get a better handle on exactly what their benefit might be.

Monitoring stem cells after transplants. Early attempts to use stem cells as therapies have been hampered by an inability to see where the cells go after transplant and if they stay the desired location and function. A team at Stanford has used some ingenious new technologies to get over this hurdle, at least in laboratory animals.

Using a homegrown technology that recently won a major innovation prize for a Stanford colleague, optogenetics, the team was able to selectively activate the transplanted cells. Then they used the older technology, functional Magnetic Resonance Imaging (fMRI), to see if the cells were working. Because cell transplants in the brain have led to some of the most difficult to interpret results in humans, they chose to work with nerve stem cells transplanted into the brains of rats. The work was partially funded by CIRM.

Starting with iPS type stem cells made from Parkinson’s patients’ skin, they inserted a gene for a protein that is sensitive to certain wavelengths of light. They then matured those cells into nerve stem cells and implanted them along with a tube that could transmit the right wavelength of light. Over the course of many months they measured the activity of the cells via fMRI with and without the light stimulation. Because the fMRI measures blood flow it by default detects active nerve cells that require more nutrients from blood than inactive cells. Senior researcher, Jin Hyung Lee described the value of this imaging in the university’s press release picked up by HealthCanal:

“If we can watch the new cells’ behaviors for weeks and months after we’ve transplanted them, we can learn — much more quickly and in a guided way rather than a trial-and-error fashion — what kind of cells to put in, exactly where to put them, and how.”

Understanding cell’s switchboard may speed therapy. Cells function by switching genes on and off. Learning which switches to hit to maximize stem cells’ ability to multiply and mature into desired cell types has occupied a significant part of the stem cell research community for years. Now, a team at the Salk Institute has shown that two known genetic switches pack an additive punch when working together.

Both those signaling processes, one called Wnt and one called Activin, are needed for stem cells to mature into specific adult tissue. The Salk team led by Kathy Jones found that when working together the two signals activate some 200 genes. Wnt seems to load the cellular equipment needed for copying the cells and Activin increases the speed and efficiency of the process. In an institute press release picked up by Science Newsline, Jones discussed the practical implications of the finding:

“Now we understand stem cell differentiation at a much finer level by seeing how these cellular signals transmit their effects in the cells. Understanding these details is important for developing more robust stem cell protocols and optimizing the efficiency of stem cell therapies.”

Charting a new, faster way to fund science and help patients

Change is never easy. In fact, sometimes it can be downright hard. But change is also essential if you want to grow, to get faster and better.

When we launched CIRM 2.0 we set out to produce a better, faster, more effective and efficient way to deliver stem cell therapies to patients with unmet medical needs. Yesterday we got a chance to see how those changes are starting to play out. And it was very encouraging.

Our Grants Working Group (GWG – we love our acronyms at CIRM. See!) is the independent panel of experts that we bring in to review all the applications for agency funding. They come from all over the US, except California, and Monday was the first chance they got to meet in person and vote on our new 2.0 applications.

The day began with a really in-depth look at how 2.0 works and how it differs quite dramatically from the old system. One of the things that always impresses me about the GWG is the extraordinary quality of the questions they ask and the level of detail they want to help them make the best possible decisions. While we would never divulge any applicant’s confidential or proprietary information, we were able to hold much of the meeting in open session – furthering our commitment to transparency.

I think Sen. Art Torres, the Vice Chair and a Patient Advocate member of our governing Board, summed it up best in a note that he sent to the CIRM Team following the meeting:

“Yesterday was a historic day for CIRM.  It was one of the best meetings I have attended and gave me renewed confidence in speaking to the public of how we continue to be responsible stewards of the taxpayers’ dollars while at the same time keeping patients as our number one priority.

I cannot speak for all the patient advocates but I think they were all impressed with the candor and meaningful dialogue that took place.

It also gave the GWG members time to bond in a very welcoming setting to express their ideas and their commitments.  I do not recall ever having a session with GWG members where they shared their personal views other than their reviews of a proposed grant.  It was revealing about how we can work more closely together with our common bonds.”

The results of the review of the first two applications under CIRM 2.0 will go to the Board for a vote on May 21, but the more important outcome will be the long-term benefit to the way we work. The in-person meeting helped the members of the GWG really understand how the changes to the way they work will speed up our ability to fund the most promising science.

This is all new, so it’s likely we’ll hit some bumps along the way. And as we roll out our new versions of 2.0 that cover funding Discovery (or basic) and Translational research later this year we’ll probably have more adjustments to make. You can’t change this much this fast and not run into problems.

But as the meeting yesterday showed so clearly, with the right team behind you even the biggest changes can be taken in stride.

Pioneering treatments: planning first-in-human stem cell clinical trials

Sometimes the reason for the most complex of projects can be boiled down to the most simple of phrases.

Dr. John Adams, Dr. Catriona Jamieson & Dr. John Zaia at the Alpha Stem Cell Clinic network meeting

(left to right) Dr. John Adams, Dr. Catriona Jamieson & Dr. John Zaia at the Alpha Stem Cell Clinic network meeting

At a meeting last week to help plan for our Alpha Stem Cell Clinic network there were lots of great presentations and discussions about the role of the network, how to structure it, what its goals would be. But in the end it was all beautifully, and succinctly, summed up by Dr. Catriona Jamieson who said: “This is great for humanity and this is why we have to do it.”

Dr. Jamieson is heading the University of California, San Diego (UCSD) part of the network. Other partners in this program are City of Hope, UC Los Angeles (UCLA) and UC Irvine (UCI). The goal is to create a network of stem cell-focused clinics that will attract and conduct high quality clinical trials. The stem cell agency is investing $24 million to help create that network.

Why do we need this? Well, stem cells are a whole new way of treating disease, one that requires new skills and expertise, and a new way of working with patients so they understand exactly what is happening.

Many of these clinical trials will be the first time these therapies have been tested in people so Shirley Johnson, RN, the Chief Nursing Officer overseeing the City of Hope program, says you need to have specially trained staff involved.

“We really look to our research patients as being our heroes and particularly our patients that are participating in those first-in-human studies. So having nurses who understand the study protocols, who understand the potential side effects that might be occurring, the symptoms that might be manifested are critical points as we think about first-in-human studies and those things that might occur, and then how best to respond to them.”

One of the reasons we are creating the Alpha Stem Cell Clinic network is because it fits in perfectly with our mission of accelerating the development of stem cell therapies to help patients with unmet medical needs. The network will not just focus on planning and carrying out clinical trials, but will also focus on how those treatments will be paid for, so that life-changing therapies won’t cost patients an arm and a leg.

Dr. John Adams, who heads the UCLA-UCI program, says there will be many obstacles to overcome, but that this is an exciting time:

“The idea behind the Alpha Clinics is to provide an infrastructure to accelerate and make it dead easy for the researchers doing this work to get their work done efficiently, effectively and faster, so that it’s more beneficial for the patients who are undergoing the treatment. And certainly it will allow us to collect more data, and better data, during the course of these clinical trials.”

The data gathered in these trials, and the lessons learned in doing them, will then be shared with others in the network to help create a system of best practices, to make it easier to carry out future clinical trials.

As Dr. John Zaia, who heads the program at City of Hope says: “This is really the beginning of a new era, the era of regenerative medicine.”

You can read more about our Alpha Stem Cell Clinic network, and find links to the individual programs here.