At World Stem Cell Summit improvements in the precision with which we can edit our genes grabs spotlight

Just a day and a half into this year’s World Stem Cell Summit in San Antonio and there have been numerous highlights. But a pair of sessions on gene editing grabbed the attention of many of the scientists at the meeting. One of the renown leaders in the field, Harvard’s George Church wowed the scientists, but I fear the heavy dose of scientific detail may have overwhelmed many of the patient advocates that make the attendee mix at this meeting special.

George Church speaking recently [Credit: PopTech.org]

George Church speaking recently [Credit: PopTech.org]

In 2013, Church first published results using a new gene-editing tool he helped perfect called CRISPR, and almost immediately it became the most talked-about tool for advancing stem cell research. As powerful as stem cells may be by themselves, in many situations, they become even more powerful—especially if you use them to deliver a gene that corrects an error in a patient’s cells. Before 2013 we had a few ways to edit genes in living cells and all were modestly effective at making the desired change and relatively specific in making only a few unwanted changes, called “off target” edits.

In some uses, particularly when cells are being modified in the lab for specific and small targets, these other editing techniques are probably OK. This is what several CIRM-funded teams (links) are doing with diseases like sickle cell anemia and HIV, where you can target blood-forming stem cells and even giving a small percentage the proper gene edit may be sufficient to cure the disease. But with something like muscular dystrophy where the gene editing would be required throughout the body and have to be done in the patient not in the lab, you need to improve the efficiency and precision.

CRISPR/Cas9 [Credit: University of California, San Francisco]

CRISPR/Cas9 [Credit: University of California, San Francisco]

After that first publication CRISPR was viewed as a home run in efficiency, taking the number of cells with the gene correction from a few percent to 50 percent or more. But it still had off-target effects. Yet only a year after the technology was introduced, a few teams developed so-called “next generation” CRISPR that comes close to perfect precision, causing an unintended edit in just one in a billion cells, by Church’s estimate.

I have never seen the full name of CRISPR spelled out in a scientific presentation, and after a visit to Wikipedia I know why. Here it is: Clustered Regularly Interspersed Short Palindromic Repeats. Basically, Church took advantage of something that occurs naturally in many bacteria. Just as we are susceptible to viruses, bacteria have their version known as phages. When those parasites integrate their DNA into the bacteria’s genes, part of the bacterial DNA forms CRISPRs that can partner with a protein called Cas to cut the phage DNA and keep the phage from hurting the host bacteria.

In a research setting, creating that “nick” in the DNA is the first step in harnessing CRISPR to insert a desired gene. So, that extreme precision in finding spots on our DNA where we want to create an opening for inserting a new gene became this valuable research tool. It can create a nick as precise as a single nucleotide base, the building blocks of our DNA.

Church and two additional speakers gave detailed descriptions about how the technology has improved and how it is being used to model disease today and is expected to be used to treat disease in the near future. An exciting future is in store.

Don Gibbons

Truth or Consequences: how to spot a liar and what to do once you catch them

Nothing undermines the credibility of science and scientists more than the retraction a high profile paper. Earlier this year there was a prime example of that when researchers at one of Japan’s most prestigious research institutions, the Riken Center for Developmental Biology in Kobe, had to retract a study that had gathered worldwide attention. The study, about a new method for creating embryonic-like stem cells called stimulus triggered acquisition of pluripotency or STAP, was discredited after it was discovered that the lead author had falsified data.

Publication retractions have increased dramatically in recent years [Credit: PMRetract]

Publication retractions have increased dramatically in recent years [Credit: PMRetract]

The STAP incident drew international coverage and condemnation and raised the question, how common is this and what can be done to combat it? A panel discussion at the World Stem Cell Summit in San Antonio, Texas entitled “Reproducibility and rigor in research: What have we learned from the STAP debacle” tackled the subject head on.

Ivan Oransky, medical journalist and the co-founder of the website Retraction Watch posed the question “Does stem cell research have a retraction problem?” He says:

“The answer to my question is yes. But so does everyone else. All of science has a retraction problem, not just stem cells.”

Oransky says the number of retractions has doubled from 2001 to 2010. One author has retracted 183 times – the record so far – but to break into the top 5 you need to have at least 50 retractions. These come from all over the world from the US to Germany and Japan and most recently Azerbaijan.

Oransky says part of the problem is the system itself. Getting your research results published is critical to advancing a career in science and those kinds of pressures force people to cut corners, take risks or even just falsify data and manipulate images in order to get a paper into a high profile journal. In most cases, journals charge a fee of several hundred to thousands of dollars to publish studies, so they have no incentive to dig too deeply into findings looking for flaws, as it might undermine their own business model.

“Some authors, more than 100, have been caught reviewing their own papers. When the journal they were submitting their paper to asked for the names of recommended reviewers they would submit the names of people who are legitimate reviewers in the field but instead of giving real email addresses they would give fake email addresses, ones they controlled so they could submit their own reviews under someone else’s name.”

What gave them away is that all the potential “reviewers” didn’t first reply and say “yes, I’ll review”, instead they responded by sending back a full review of the paper, raising suspicions and ultimately to detection.

Graham Parker, a researcher at Wayne State University School of Medicine and the editor of Stem Cell and Development says spotting the problem is not always easy:

“As an editor I regard scientific misconduct as fabrication, falsification or plagiarism of data but there are lots of other areas where it’s not always so clear – there are often shades of gray”

He says researchers may make an honest mistake, or include duplicative images and in those cases should be allowed to fix the problems without any stigma attached. But when serious cases of falsification of data are uncovered they can have a big impact by retarding scientific progress and sapping public confidence in the field as a whole.

Jeanne Loring, a stem cell scientist at The Scripps Research Institute and a recipient of funding from CIRM, says the STAP incident was actually a sign of progress in this area. Ten years ago when a Korean researcher named Hwang Woo-Suk claimed to have cloned human embryos it took more than a year before he was found to have falsified the data. But in the STAP case it took a little over a week for other researchers to start raising red flags:

“One of the real heroes in this story is Paul Knoepfler (a CIRM-funded researcher at UC Davis) who takes on difficult issues in his blog. It took Paul just 8 days to post a request for people to crowdsource this study, asking people who were trying to replicate the findings to report their results – and they did, showing they failed over and over again”

Parker said it’s getting easier for editors and others in the field to double check data in studies. For example new software programs allow him to quickly check submitted manuscripts for plagiarism. And he says there is a growing number of people who enjoy looking for problems.

“Nowadays it’s so easy for people to dig very deeply into papers and check up on every aspect of it, from the content to the methodology to the images they use and whether those images were in any way manipulated to create a false impression. Once they find a problem with one paper they’ll dig back through papers in that scientist’s past to see if they can find other problems dating back years that were never found at the time.”

He says that in most cases researchers caught falsifying data or deliberately misleading journals faced few consequences:

“Often the consequences of misconduct are very mild, the equivalent of a slap on the wrist, which does not discourage others from trying to do the same.”

Each panel member says that tougher penalties are needed. For example, in extreme cases a threat of criminal action could be warranted, if the falsified research could lead to serious consequences for patients.

But the panel ended on an encouraging note. Oransky says, for example, that medical journals are now paying more attention and imposing stricter rules and he says there’s even scientific evidence that “doing the right thing might pay off.”

“One study recently showed that if you made an honest error and corrected it publicly not only does the stigma of retraction not apply to you, you don’t get a decrease in your citations—you actually get an increase. So we’d like to think that doing the right thing is a good thing and might actually be a positive thing.”

Taking Promising Therapies out of the Lab and into People: Tips from Experts at the World Stem Cell Summit on How to Succeed

Having a great idea for a stem cell therapy is the easy part. Getting it to work in the lab is tougher. But sometimes the toughest part of all is getting it out of the lab and into clinical trials in patients. That’s natural and sensible, after all we need to make sure that something seems safe before even trying it in people. But how do you overcome all the challenges you face along the way? That was the topic of one of the panel discussions at the World Stem Cell Summit in San Antonio, Texas.

Rick Blume is the Managing Director at Excel Venture Management, and someone with decades of experience in investing in healthcare companies. He says researchers face numerous hurdles in trying to move even the most promising therapies through the approval and regulatory process, only some of which are medical. Blume says:

“Great ideas can become great companies. And good Venture Capitalists (VCs) can help with that process, but the researchers have to overcome technical, funding and logistical hurdles before VCs are usually ready to move in and help.”

Of course that’s where agencies and organizations like CIRM come in. We help fund the early stage research, helping researchers overcome those hurdles and getting promising therapies to a point where VCs and other large investors are willing to step in.

Left to right: Geoff Crouse CEO of Cord Blood Registry, C. Randal Mills, President and CEO of CIRM, Rick Blume of Excel Venture Management and Anthony Atala of Wake Forest University Medical Center

Left to right: Geoff Crouse CEO of Cord Blood Registry, C. Randal Mills, President and CEO of CIRM, Rick Blume of Excel Venture Management and Anthony Atala of Wake Forest University Medical Center

Geoff Crouse, the CEO of the Cord Blood Registry, says researchers need to be increasingly imaginative when looking for funding these days.

“While Federal funding for this kind of research is drying up, there are alternatives such as CIRM and philanthropic investors who are not just seeking to make active investments but are also trying to change the world, so they offer alternatives to more traditional sources of funding. You have to look broadly at your funding opportunities and see what you want to do.”

C. Randal Mills, the President and CEO of CIRM said too many people get caught up looking at the number of challenges that any project faces when it starts out:

“The single most important thing that you need to do is to show that the treatment works in people with unmet medical needs, that it is safe. If you can do that, all the other problems, the cost of the therapy, how to market it, how to get reimbursed for it, those will all be resolved in time. But first you have to make it work, then you can make it work better and more efficiently.”

The panel all agreed that one of the areas that needs attention is the approval and regulatory process saying the Food and Drug Administration (FDA) the regulatory body governing this field, needs to adjust its basic “one size fits all” paradigm.”

Mills says the FDA is in a difficult position:

“Everyone wants three things; they want fast drugs, they want cheap drugs and they want perfect drugs. The problem is you can’t have all three. You can have two but not all three and that puts the FDA into an almost impossible position because if therapies aren’t approved quickly they are criticized but if they are approved and later show problems then the FDA is criticized again.”

Often the easiest way to get a traditional drug therapy approved for use is to ask for a “humanitarian exemption”, particularly for an orphan disease that has a relatively small number of people suffering from it and no alternative therapies. But when it comes to more complex products knows as biologics, which includes stem cell therapies, this humanitarian exemption does not exist making approval much harder to obtain, slowing down the field.

Mills says other countries, such as Japan, have made adjustments to the way they regulate new therapies such as stem cells and he hopes the FDA will learn from that and make similar modifications to the way they see these therapies.

All three panelists were optimistic that the field is making good progress, and will continue to advance. Good news for the many patient advocates attending the World Stem Cell Summit who are waiting for treatments for themselves or loved ones.

At World Stem Cell Summit: Why results in trials repairing hearts are so uneven

Just as no two people are the same, neither are the cells in their bone marrow, the most common source of stem cells in clinical trials trying to repair damage after a heart attack. Doris Taylor of the Texas Heart Institute in Houston, which is just a couple hours drive from the site of this year’s World Stem Cell Summit in San Antonio, gave a key note address this morning that offered some good reasons for the variable and often disappointing results in those trials, as well as some ways to improve on those results.

THI's Dr. Doris Taylor

THI’s Dr. Doris Taylor

The cells given in a transplant derived from the patient’s own bone marrow contain just a few percent stem cells and a mix of adult cells, but for both the stem and adult cells the mix is highly variable. Taylor said that in essence we are giving each patient a different drug. She discussed a series of early clinical trials in which cell samples from each patient were banked at the National Heart and Lung and Blood Institute. There they could do genetic and other analysis on the cells and compare that data with how each individual patient faired.

In looking at the few patients in each trial that did better on any one of three measures of improved heart function, they were indeed able to find certain markers that predicted better outcome. In particular they looked at “triple responders,” those who improved in all three measures of heart function. They found there were both certain types of adult cells and certain types of stem cells that seemed to result in improved heart health.

They also found that two of the strongest predictors were gender and age. Women generally develop degenerative diseases of aging like heart disease at an older age than men and since many consider aging to be a failure of our adult stem cells, it would make sense that women have healthier stem cells.

Taylor went on to discuss ways to use this knowledge to improve therapy outcomes. One way would be to select for the more potent cells identified in the NHLBI analysis. She mentioned a couple trials that did show better outcomes using cells derived from heart tissue. One of those is work that CIRM funds at Cedars-Sinai in Los Angeles.

Another option is replace the whole heart and she closed with a review of what is probably her best-known work, trying to just that. In rats and pigs, she has taken donor hearts and used soap-like solutions to wash away the living cells so that all that is left behind are the proteins and sugars that make of the matrix between cells. She then repopulates the scaffolds that still have the outlines of the chambers of the heart and the blood vessels that feed them, with cells from the recipient animal. She has achieved partially functional organs but not fully functional ones. She—along with other teams around the world—is working on the remaining hurdles to get a heart suitable for transplant.

Don Gibbons

Searching for a Cure for HIV/AIDS: Stem Cells and World AIDS Day

World-AIDS-Day

It’s been 26 years since the first World AIDS Day was held in 1988—and the progress that the international scientific community has made towards eradicating the disease has been unparalleled. But there is much more work to be done.

One of the most promising areas of HIV/AIDS research has been in the field of regenerative medicine. As you observe World AIDS Day today, we invite you to take a look at some recent advances from CIRM-funded scientists and programs that are well on their way to finding ways to slow, halt and prevent the spread of HIV/AIDS:

Calimmune’s stem cell gene modification study continues to enroll patients, show promise:
Calimmune Approved to Treat Second Group in HIV Stem Cell Gene Modification Study

Is a cure for HIV/AIDS possible? Last year’s public forum discusses the latest on HIV cure research:


Town Hall: HIV Cure Research

The Stem Cell Agency’s HIV/AIDS Fact Sheet summarizes the latest advances in regenerative medicine to slow the spread of the disease.

And for more on World AIDS Day, follow #WorldAIDSDay on Twitter and visit WorldAIDSDay.org.

10 Years/10 Therapies: 10 Years after its Founding CIRM will have 10 Therapies Approved for Clinical Trials

In 2004, when 59 percent of California voters approved the creation of CIRM, our state embarked on an unprecedented experiment: providing concentrated funding to a new, promising area of research. The goal: accelerate the process of getting therapies to patients, especially those with unmet medical needs.

Having 10 potential treatments expected to be approved for clinical trials by the end of this year is no small feat. Indeed, it is viewed by many in the industry as a clear acceleration of the normal pace of discovery. Here are our first 10 treatments to be approved for testing in patients.

HIV/AIDS. The company Calimmune is genetically modifying patients’ own blood-forming stem cells so that they can produce immune cells—the ones normally destroyed by the virus—that cannot be infected by the virus. It is hoped this will allow the patients to clear their systems of the virus, effectively curing the disease.

Spinal cord injury patient advocate Katie Sharify is optimistic about the latest clinical trial led by Asterias Biotherapeutics.

Spinal cord injury patient advocate Katie Sharify is optimistic about the clinical trial led by Asterias Biotherapeutics.

Spinal Cord Injury. The company Asterias Biotherapeutics uses cells derived from embryonic stem cells to heal the spinal cord at the site of injury. They mature the stem cells into cells called oligodendrocyte precursor cells that are injected at the site of injury where it is hoped they can repair the insulating layer, called myelin, that normally protects the nerves in the spinal cord.

Heart Disease. The company Capricor is using donor cells derived from heart stem cells to treat patients developing heart failure after a heart attack. In early studies the cells appear to reduce scar tissue, promote blood vessel growth and improve heart function.

Solid Tumors. A team at the University of California, Los Angeles, has developed a drug that seeks out and destroys cancer stem cells, which are considered by many to be the reason cancers resist treatment and recur. It is believed that eliminating the cancer stem cells may lead to long-term cures.

Leukemia. A team at the University of California, San Diego, is using a protein called an antibody to target cancer stem cells. The antibody senses and attaches to a protein on the surface of cancer stem cells. That disables the protein, which slows the growth of the leukemia and makes it more vulnerable to other anti-cancer drugs.

Sickle Cell Anemia. A team at the University of California, Los Angeles, is genetically modifying a patient’s own blood stem cells so they will produce a correct version of hemoglobin, the oxygen carrying protein that is mutated in these patients, which causes an abnormal sickle-like shape to the red blood cells. These misshapen cells lead to dangerous blood clots and debilitating pain The genetically modified stem cells will be given back to the patient to create a new sickle cell-free blood supply.

Solid Tumors. A team at Stanford University is using a molecule known as an antibody to target cancer stem cells. This antibody can recognize a protein the cancer stem cells carry on their cell surface. The cancer cells use that protein to evade the component of our immune system that routinely destroys tumors. By disabling this protein the team hopes to empower the body’s own immune system to attack and destroy the cancer stem cells.

Diabetes. The company Viacyte is growing cells in a permeable pouch that when implanted under the skin can sense blood sugar and produce the levels of insulin needed to eliminate the symptoms of diabetes. They start with embryonic stem cells, mature them part way to becoming pancreas tissues and insert them into the permeable pouch. When transplanted in the patient, the cells fully develop into the cells needed for proper metabolism of sugar and restore it to a healthy level.

HIV/AIDS. A team at The City of Hope is genetically modifying patients’ own blood-forming stem cells so that they can produce immune cells—the ones normally destroyed by the virus—that cannot be infected by the virus. It is hoped this will allow the patients to clear their systems of the virus, effectively curing the disease

Blindness. A team at the University of Southern California is using cells derived from embryonic stem cell and a scaffold to replace cells damaged in Age-related Macular Degeneration (AMD), the leading cause of blindness in the elderly. The therapy starts with embryonic stem cells that have been matured into a type of cell lost in AMD and places them on a single layer synthetic scaffold. This sheet of cells is inserted surgically into the back of the eye to replace the damaged cells that are needed to maintain healthy photoreceptors in the retina.

UCLA team cures infants of often-fatal “bubble baby” disease by inserting gene in their stem cells; sickle cell disease is next target

Poopy diapers, ear-splitting cries, and sleepless nights: sure, the first few weeks of parenthood are grueling but those other moments of cuddling and kissing your little baby are pure bliss.

The bubble boy.  Born in 1971 with SCID, David Vetter lived in a sterile bubble to avoid outside germs that could kill him. He died in 1984 at 12 due to complications from a bone marrow transplant. [Credit: Baylor College of Medicine Archives]

The bubble boy. Born in 1971 with SCID, David Vetter lived in a sterile bubble to avoid outside germs that could kill him. He died in 1984 at 12 due to complications from a bone marrow transplant. [Credit: Baylor College of Medicine Archives]

That wasn’t the case for Alysia and Christian Padilla-Vacarro of Corona, California. Close contact with their infant daughter Evangelina, born in 2012, was off limits. She was diagnosed with a genetic disease that left her with no immune system and no ability to fight off infections so even a minor cold could kill her.

Evangelina was born with Severe Combined Immunodeficiency (SCID) also called “bubble baby” disease, a term coined in the 1970s when the only way to manage the disease was isolating the child in a super clean environment to avoid exposure to germs. Bone marrow transplants from a matched sibling offer a cure but many kids don’t have a match, which makes a transplant very risky. Sadly, many SCID infants die within the first year of life.

Until now, that is.

Today, a UCLA research team led by Donald Kohn, M.D., announced a stunning breakthrough cure that saved Evangelina’s life and all 18 children who have so far participated in the clinical trial. Kohn—the director of UCLA’s Human Gene Medicine Program—described the treatment strategy in a video interview with CIRM (watch the video below):

“We collect some of the baby’s own bone marrow, isolate the [blood] stem cells, add the gene that they’re missing that their immune system needs and then transplant the cells back to them. “

Inserting the missing gene, called ADA, into the blood stem cells restores the cells’ ability to produce a healthy immune system. And since the cells originally came from the infant, there’s no worry about the possible life-threatening complications from receiving non-matched donor cells.

This breakthrough didn’t occur overnight. Kohn and colleagues have been plugging away for over twenty years carrying out trials, observing their limitations and going back to lab to improve the technology. Their dedication has paid off. As Kohn states in a press release:

“All of the children with SCID that I have treated in these stem cell clinical trials would have died in a year or less without this gene therapy, instead they are all thriving with fully functioning immune systems.”

Alysia Padilla-Vacarro and daughter Evangelina on the day of her gene therapy treatment. Evangelina, now two years old, has had her immune system restored and lives a healthy and normal life. [Credit: UCLA Broad Center of Regenerative Medicine and Stem Cell Research.]

Alysia Padilla-Vacarro and daughter Evangelina on the day of her gene therapy treatment. Evangelina, now two years old, has had her immune system restored and lives a healthy and normal life. [Credit: UCLA Broad Center of Regenerative Medicine and Stem Cell Research.]

For the Padilla-Vacarro family, the dark days after Evangelina’s grave diagnosis have given way to a bright future. Alysia, Evangelina’s mom, poignantly recalled her daughter’s initial recovery:

”It was only around six weeks after the procedure when Dr. Kohn told us Evangelina can finally be taken outside. To finally kiss your child on the lips, to hold her, it’s impossible to describe what a gift that is. I gave birth to my daughter, but Dr. Kohn gave my baby life.”

The team’s next step is to get approval by the Food and Drug Administration (FDA) to provide this treatment to all SCID infants missing the ADA gene.

At the same time, Kohn and colleagues are adapting this treatment approach to cure sickle cell disease, a genetic disease that leads to sickle shaped red blood cells. These misshapen cells are prone to clumping causing debilitating pain, risk of stroke, organ damage and a shortened life span. CIRM is providing over $13 million in funding to support the UCLA team’s clinical trial set to start early next year.

For more information about CIRM-funded sickle cell disease research, visit our fact sheet.

Entrepreneurship and Education

Guest author Neil Littman is CIRM’s Business Development Officer.

CIRM works closely with UCSF on a number of initiatives, from providing funding to academic investigators to jointly hosting events such as the recent CIRM Showcase with J-Labs held at the Mission Bay campus.

Beyond our joint initiatives, UCSF also provides many other valuable resources and educational opportunities to the life sciences community in the Bay Area. For instance, I was a mentor in UCSF’s “Idea to IPO” class which focused on helping students translate concepts into a commercializable product and viable business.

Another opportunity that may be of interest to all you budding entrepreneurs is UCSF’s Lean LaunchPad course, which kicks off in January (application deadline is Nov 19th). The course teaches…

“scientists and clinicians how to assess whether the idea or technology they have can serve as the basis of a business. The focus is on the marketplace where you must validate that your idea has value in order to move into the commercial world.”

See more at: Lean Launchpad for Life Sciences & Healthcare.

The course is being run out of the Entrepreneurship Center at UCSF, which is a division of the UCSF Office of Innovation, Technology & Alliances (ITA).

Ideas and Energy Reveal Surprises at Stem Cell Showcase

Janssen, the company within the pharmaceutical giant Johnson & Johnson responsible for much of its research and development, has a branch in the Bay Area called J Labs. It seeks to foster innovation in all sectors of biomedical research. One piece of that effort brings together innovators for monthly gatherings to exchange ideas and network. The events have an upbeat sense of energy so it was exciting when they invited CIRM to put together an all-day session dubbed: CIRM Showcase: Accelerating Stem Cell Treatments to Patients.

logo

The resulting showcase yesterday had that energy. But for someone who knows the CIRM portfolio of projects backward and forward, I thought, there were a few pleasant surprises. Perhaps the most exciting news came from Linda Marban, CEO of Capricor, the company CIRM is funding to complete a clinical trial in patients with weakened hearts after a heart attack. She disclosed that the company’s next target is the heart remodeling that is the cause of death in most boys with Duchenne muscular dystrophy. She said some early data would be released at the American Heart Association meeting in Chicago in two weeks.

Another bit of news—most exciting for science wonks—came from the biotech company Sangamo that CIRM funds to develop genetically modified blood stem cells as therapy for two diseases, HIV and beta thalassemia. The firm has developed a molecular scissors called a zinc finger nuclease that can splice the DNA that makes our genes. I knew the technique was pretty precise, but Curt Herberts from the company said they had perfected it to where it could get down to a single base pair—a single link in the chain that makes up our DNA. This greatly reduces the chances for any unintended effects of the genetic manipulation.

Two advances I learned about were in using iPS type stem cells as models for disease and for discovery of traditional drugs to treat those diseases. Ashkan Javaherian, from Steve Finkbeiner’s lab at the Gladstone Institutes, described some results with the robotic microscope they have developed that lets them screen hundreds of molecules on neurons grown from iPS cells reprogrammed from patients with specific diseases. Looking just at compounds already approved by the Food and Drug Administration (FDA), ones that could be put in the clinic quickly, they found four that reduced the degradation normally seen in neurons grown from patients with Huntington’s disease.

Similarly, Joseph Wu of Stanford described his work with cells from families with various genetic heart disorders. In addition to getting individualized information from the patient-specific cells, he said they could now take it one step further and sequence the entire DNA of the cells for just $500, yielding the chance to find out exactly what mutations were causing the disease. He said it was a big step towards truly personalized medicine and to developing therapies for various racial groups that respond differently to drugs.

The day began with our President and CEO C. Randall Mills detailing his plans for a nimbler, more responsive CIRM he has dubbed CIRM 2.0. This crowd seemed thrilled with his plan for an open call for applications so that they could come in with a request when they are ready instead of forcing them into a premature application for funding because the window might not open for another year or two.

One bit of trivia drove home how difficult the entire process of moving innovative therapies into the clinic can be. Paul Laikind, CEO of ViaCyte, the company CIRM has provided more than $50 million to develop a diabetes therapy, noted the size of the application they sent to the FDA: 8,500 pages. Kind of says it all.

Don Gibbons

What everybody needs to know about CIRM: where has the money gone

It’s been almost ten years since the voters of California created the Stem Cell Agency when they overwhelmingly approved Proposition 71, providing us $3 billion to help fund stem cell research.

In the last ten years we have made great progress – we will have ten projects that we are funding in or approved to begin clinical trials by the end of this year, a really quite remarkable achievement – but clearly we still have a long way to go. However, it’s appropriate as we approach our tenth anniversary to take a look at how we have spent the money, and how much we have left.

Of the $3 billion Prop 71 generates around $2.75 billion was set aside to be awarded to research, build laboratories etc. The rest was earmarked for things such as staff and administration to help oversee the funding and awards.

Of the research pool here’s how the numbers break down so far:

  • $1.9B awarded
  • $1.4B spent
  • $873M not awarded

So what’s the difference between awarded and spent? Well, unlike some funding agencies when we make an award we don’t hand the researcher all the cash at once and say “let us know what you find.” Instead we set a series of targets or milestones that they have to reach and they only get the next installment of the award as they meet each milestone. The idea is to fund research that is on track to meet its goals. If it stops meetings its goals, we stop funding it.

Right now our Board has awarded $1.9B to different institutions, companies and researchers but only $1.4B of that has gone out. And of the remainder we estimate that we will get around $100M back either from cost savings as the projects progress or from programs that are cancelled because they failed to meet their goals.

So we have approximately $1B for our Board to award to new research, which means at our current rate of spending we’ll have enough money to be able to continue funding new projects until around 2020. Because these are multi-year projects we will continue funding them till around 2023 when those projects end and, theoretically at least, we run out of money.

But we are already working hard to try and ensure that the well doesn’t run dry, and that we are able to develop other sources of funding so we can continue to support this work. Without us many of these projects are at risk of dying. Having worked so hard to get these projects to the point where they are ready to move out of the laboratory and into clinical trials in people we don’t want to see them fall by the wayside for lack of support.

Of the $1.9B we have awarded, that has gone to 668 awards spread out over five different categories:

CIRM spending Oct 2014

Increasingly our focus is on moving projects out of the lab and into people, and in those categories – called ‘translational’ and ‘clinical’ – we have awarded almost $630M in funding for more than 80 active programs.

Untitled

Under our new CIRM 2.0 plan we hope to speed up the number of projects moving into clinical trials. You can read more about how we plan on doing there in this blog.

It took Jonas Salk almost 15 years to develop a vaccine for polio but those years of hard work ended up saving millions of lives. We are working hard to try and achieve similar results on dozens of different fronts, with dozens of different diseases. That’s why, in the words of our President & CEO Randy Mills, we come to work every day as if lives depend on us, because lives depend on us.