The search for a cure: how stem cells could eradicate the AIDS virus

It’s hard to overstate just how devastating the AIDS crisis was at its peak in the U.S. – and still is today in many parts of the world. In 1995 almost 51,000 Americans died from the disease, the numbers of new cases were at almost record highs, and there were few effective therapies against the virus.

HIV/AIDS medications

HIV/AIDS medications

Today that picture is very different. New medications and combination therapies have helped reduce the death rate, in some cases turning HIV into a chronic rather than fatal condition. But even now there is no cure.

That’s why the news that the Food and Drug Administration (FDA) has approved a clinical trial, that we are funding, aimed at eradicating HIV in the body, was so welcome. This could be an important step towards the Holy Grail of AIDS therapies, curing the disease.

The project is headed by Dr. John Zaia at City of Hope near Los Angeles. The team, with researchers from Keck Medicine of the University of Southern California (USC) and Sangamo BioSciences, plans on using an individual’s own stem cells to beat the virus.  They will remove some blood stem cells from HIV-infected individuals, then treat them with zinc finger nucleases (ZFNs), a kind of molecular scissors, snipping off a protein the AIDS virus needs to infect those cells.

It’s hoped the re-engineered stem cells, when returned to the body, will help create a new blood and immune system that is resistant to the virus. And if the virus can’t infect any new immune cells it could, theoretically, die off. Check out the video we produced a few years back about the project:

Studies in the lab show this approach holds a lot of promise. In a news release announcing the start of the clinical trial, Dr. Zaia said now it’s time to see if it will work in people:

“While we have a number of drugs that are effective in holding HIV at bay, we have nothing that cures it. In addition, for many patients, these medications come with significant long-term problems so there is a real need for a therapy that can help eradicate the virus from a patient completely. That is where our work is focused.”

Like all Phase 1 trials this one is focused on making sure this approach is safe for people, and identifying what, if any, side-effects there are from the treatment. The first group of patients to be treated consists of people with HIV/AIDS who have not responded well to the existing medications.

This is the second trial that CIRM is funding focused on curing HIV/AIDS. Our first, involving the company Calimmune, began its human clinical trial in July 2013. You can read more about that work here.

We know that the road to a cure will not be simple or straightforward. There have been too many false claims of cures or miracle therapies over the years for any of us to want to fall victim to hope and hype. It may even be that the most realistic goal for these approaches is what is called a “functional cure”, one that doesn’t eliminate the virus completely but does eliminate the need to take antiretroviral pills every day.

But when compared to the dark days of 1995, a functional cure is a world away from certain death.

How the human genome is unlocking some of the secrets of stem cells, hopefully leading to new treatments

A little over a year ago we set aside $40 million to study how variations in the human genome – the complete map of our genetic information – can affect our ability to use stem cells to treat a wide variety of diseases and disorders.

Human-Genome-Project_finalThat money helped set up the Stanford/Salk Center of Excellence in Stem Cell Genomics (CESCG) with a goal of using genomic analysis to better understand how stem cells change as they grow and become different kinds of cells, and then use that knowledge to develop new treatments for a wide variety of conditions.

Now the CESCG has just announced it is investing $11.6 million on seven different projects aimed at gaining a deeper understanding of deadly or disabling diseases and conditions, such as heart disease and autism.

As Stanford’s Dr. Michael Snyder, a co-Principal Investigator on the project, said in a news release, a major part of CESCG’s mission is to “establish a Collaborative Research Program (CRP) to support the genomics research needs of stem cell investigators in California,”

‘We don’t just provide funds we also partner with the individual researchers, providing them with the support, expertise and resources they need to conduct successful genomics analyses. We received 30 applications from throughout the State, and after peer review 7 projects were identified as the best new collaborations for the Center.”

So how does this advance stem cell science? Well, in the past researchers often depended on animal models for their work; but because results in animals don’t always translate when applied to people this was not always an effective way to work. At the University of California, San Francisco and the University of California, Los Angeles researchers Arnold Kriegstein and Gay Crooks are using genomics to better understand normal human cell identities in the brain (UCSF) and the blood (UCLA) and then applying that knowledge to help develop more accurate and more detailed stem cell-based models for us to study.

Jonathan Thomas, the Chair of our Board, says one of the best ways to do great science, is to create a great team:

“The goal of the Board in creating this program and bringing together this group of researchers was to accelerate our fundamental understanding of human biology and the ways that disease work. That knowledge will help point the way not just to new treatments but also, hopefully, to ways that those treatments can potentially be tailored to meet the needs of individual patients.”

Meryl Streep, Lindsay Lohan and the importance of staying above the fray in science communications

Carl Sagan: photo courtesy Brainpickings.org

Carl Sagan: photo courtesy Brainpickings.org

Carl Sagan, the astronomer and cosmologist (among many other things) once said: “We live in a society absolutely dependent on science and technology, and yet have cleverly arranged things so that almost no one understands science and technology. That’s a clear prescription for disaster.”

The goal of two panel discussions at the American Association for the Advancement of Science (AAAS) conference in San Jose last week was to find ways to change that: to get the public to both understand and care more about science and technology; and to get scientists to do a better job of explaining both to them.

The first challenge of course is finding scientists who want to be part of this public conversation. Dr. Nalini Nadkarni, an ecologist who studies rain forests, said for young scientists in particular it’s not just a matter of having the right skills, it’s also a matter of finding the time:

“One of the challenges of scientific engagement is that just being a scientist is a full-time job, and it’s hard to think about doing public engagement when you are trying to build a career.”

Dr. Anthony Dudo, who studies the intersection of science, media and society, says one thing universities can do is encourage outreach and engagement, maybe even make it a factor in a teacher getting tenure. He says there are a lot of researchers who are happy to do this kind of outreach – either through public talks or media interviews – and they do it for all sorts of reasons.

“Many do it because it’s something they enjoy, they consider it a civic duty, something that sparks public interest in science and raises awareness about their field. In addition some say it can enhance their own scientific reputation and increase visibility for funding.”

But there is a risk. Some scientists reported facing a backlash from colleagues who felt they were trying to hog the limelight. They fell victim to what is called the “Carl Sagan” effect, which holds that if someone is spending that much time and effort communicating science to the public they must not be a very good scientist to start with.

No one could accuse Stanford’s Dr. Noah Diffenbaugh of not being a good scientist – he specializes in studying climate change and you can read his extensive resume here –  but he is also a gifted communicator, something he says he feels is his duty:

“I feel it is my responsibility to answer questions from the public when asked, because my research group is publicly funded by taxpayer dollars through agencies like the NSF. And as a public citizen I feel responsible that if we are having a public dialogue about climate change that I should be part of that dialogue.”

But he says he is very careful to avoid taking sides in the debate. He tells of an interview he once heard where Oscar-winning actress Meryl Streep talked about the importance of keeping her personal life and beliefs private (as opposed to Lindsay Lohan’s very public private life). Streep says as an actress she wants people to be able to look at her on screen and focus on the character she is playing, and not be distracted by thinking about any very public shenanigans she may have been involved in. Diffenbaugh says a scientist’s credibility depends on them doing the same:

“I stick to the facts and don’t express personal opinions or offer advocacy positions. I feel strong that in public discussions about climate change that someone in the conversation needs to be focused on evidence. It’s a role that scientists are fundamentally equipped to play.”

But even the best communicators are finding it increasingly hard to get their message into the media these days. Fewer and fewer newspapers or TV stations have skilled, experienced health and science writers, which makes it difficult to reach the public.

Lisa Krieger is an award-winning science journalist at the San Jose Mercury News. She says she finds it challenging getting stories she wants to write into the paper because she is competing for shrinking space against stories that might seem more relevant to local readers:

“Basic science is hard to cover because readers want to know how it will benefit them directly and sometimes these things are years, or even decades, away from having any real impact on people. And that’s a hard sell to an editor to get those kinds of stories into the paper.”

Krieger says the key to getting the message out is making it personal, tell stories about real people, about the real impact something could have on someone.

While acknowledging the challenges, and risks, of being a public voice and face for science – particularly when there is so much political polarization around science these days – everyone agreed that we need more scientists who are willing and able to talk about their work in ways that will engage the public, help them understand what is being done and why they should care.

For Carl Sagan (yes, him again) the reason why scientists should engage with the public was simple; to share knowledge about the wonders of the world we live in.

“It is sometimes said that scientists are unromantic, that their passion to figure out robs the world of beauty and mystery. But is it not stirring to understand how the world actually works—that white light is made of colors, that color is the way we perceive the wavelengths of light, that transparent air reflects light, that in so doing it discriminates among the waves, and that the sky is blue for the same reason that the sunset is red? It does no harm to the romance of the sunset to know a little bit about it.”

Peering inside the brain: how stem cells could help turn skin into therapies for dementia

To truly understand a disease you need to be able to see how it works, how it causes our body to act in ways that it shouldn’t. In cancer, for example, you can take cells from a tumor and observe them under a microscope to see what is going on. But with diseases of the brain it’s much harder. You can’t just open someone’s skull to grab some cells to study. However, now we have new tools that enable us to skip the skull-opening bit, and examine brain cells in people with diseases like dementia, to see what’s going wrong, and maybe even to get some ideas on how to make it right.

AF_neuronTHMito(2)_webThe latest example of this comes from researchers in Belgium who have developed a new strategy for treating patients with an inherited form of dementia. They used the induced pluripotent stem cell (iPSC) method, taking take skin cells from patients with frontotemporal dementia, and turning them into neurons, the kind of brain cell damaged by the disease. They were then able to study those neurons for clues as to what was happening inside the brain.

The study is reported in the journal Stem Cell Reports, and in an accompanying news release the senior author, Catherine Verfaillie, says this approach allows them to study problems in the brain in ways that weren’t possible before.

“iPSC models can now be used to better understand dementia, and in particular frontotemporal dementia, and might lead to the development of drugs that can curtail or slow down the degeneration of cortical neurons.”

The researchers identified problems with a particular signaling pathway in the brain, Wnt, which plays an important role in the development of neurons. In patients with frontotemporal dementia, the neurons weren’t able to mature into cortical neurons, which play a key role in enabling thought, perception and voluntary movement. However, by genetically correcting that problem they were able to restore the ability of the neurons to turn into cortical neurons.

Philip Van Damme, a lead researcher on the project, says this may open up possible ways to treat the problem.

“Our findings suggest that signaling events required for neurodevelopment may also play major roles in neurodegeneration. Targeting such pathways, as for instance the Wnt pathway presented in this study, may result in the creation of novel therapeutic approaches for frontotemporal dementia.”

A look at 2014: some of the lowlights of stem cell research this past year

It’s been quite a year in stem cell research. Here at the stem cell agency eight projects that we are funding have been approved for clinical trials and several more hope to get approval in early 2015. And Dr. Don Kohn and his team at UCLA announced that they have effectively cured Severe Combined Immunodeficiency or SCID  a fatal disease that leaves infants with no immune system.

But the news hasn’t been all good. A number of high profile retractions of studies published in prestigious journals have drawn attention to some of the less lovely aspects of science. There are many reasons why a researcher or scientific journal decides to retract a study – falsified data, inability of others to reproduce the findings etc. – but the end result is always the same, a stain on the reputation of science in general.

Of course the only thing worse than a retraction is bad science that is not retracted. That’s why websites such as Retraction Watch are so important. They keep an eye on the field and help draw attention to questionable papers (in all areas of science, not just stem cell research).

Ivan Oransky of Retraction Watch

Ivan Oransky of Retraction Watch

The two founders of the site, Evan Marcus and Ivan Oransky, do a remarkable job of highlighting work that doesn’t stand up to closer scrutiny. This year they worked with the magazine Science to highlight The Top 10 Retractions of 2014.  Sadly, two of the top 10 – including the number one story of the year – concern stem cell research.

The list is a reminder, as we look forward to 2015 for more progress in the field, that we need to always check the credibility of studies or sources we are using. Sometimes something that seems too good to be true, is too good to be true.

Tomorrow, we’ll take a look at the flip side of this discussion, the “Biggest Scientific Breakthroughs of 2014”. It’s always good to end the year on a positive note.

Maintaining the momentum: a good start but CIRM 2.0 is just the first step

Sir Isaac Newton

Sir Isaac Newton

Newton’s First Law of Physics states that an object either remains at rest or continues to move at a constant velocity unless acted upon by an external force. Well, for the stem cell agency the external force was an exercise in thinking differently about how we do business. That resulted in our governing Board approving CIRM 2.0 yesterday. And we intend to keep that momentum going for as long as we can.

CIRM 2.0 is a streamlined process that will make it easier and faster to apply for funding from the stem cell agency, and is designed to attract high quality clinical stage projects that are ready to start within 45 days of being approved for funding.

As our President and CEO Dr. C. Randal Mills said in a news release:

“Our mission is to accelerate the development of stem cell treatments for patients with unmet medical needs. With many of these diseases, time lost waiting for a treatment means lives lost. We must continue to find new and innovative ways to speed up our process and make it easier to get promising therapies into clinical trials, and to give them all the support they need to be successful. That’s why we undertook this radical overhaul of the way we do business.”

In the past it could take up to two years for a researcher or company to move from applying for funding to getting the money as part of an approved contract. CIRM 2.0 simplifies and accelerates the process, cutting that two years down to just four months. And instead of just one single round of funding with an application deadline every 12-to-18 months, CIRM 2.0 will have an open application process for clinical stage programs with deadlines every month. That means companies and researchers can apply when they are ready and won’t have to try and rush an application in prematurely, for fear it could be another year or more before the chance comes around again.

It’s a big change in the way we work and as Dr. Mills told the Board at yesterday’s meeting, there are bound to be problems:

“There will be bumps in the road, you can’t make radical changes of this nature and scope without running into problems. I know that, my team knows that and we are ready to handle whatever unforeseen consequences come up.”

We plan on monitoring 2.0 as we unveil it, constantly checking to see what’s working and to fix what isn’t. In the short term we will use several measures of how well it’s working such as how many high quality applications we get, how quickly we can move these applications through the approvals process and how long it takes to get successful applicants their money. In the long term the best indication of success will be the quality of the programs we fund and how well they do in completing clinical trials.

This first phase of CIRM 2.0 will cover funding for clinical work but it will later be expanded to include discovery (also known as basic research) and translational research (moving promising discovery research to the clinic). But as Dr. Mills says, even while we are implementing CIRM 2.0 we are already thinking about the next step.

“Soon as this is done we have to start working on how we can improve CIRM 2.0 and keep that sense of urgency and innovation in front of us so that we always look to build a better product and fulfill our mission in a better way. Because there are many sick people out there looking to us for help and until that changes we need to be always looking to improve. Which is why as soon as CIRM 2.0 is done, we’re looking to create CIRM 3.0”

Ten at ten at the stem cell agency: sharing the good news about progress from the bench to the bedside

Ten years ago this month the voters of California overwhelmingly approved Proposition 71, creating the state’s stem cell agency, the California Institute for Regenerative Medicine, and providing $3 billion to fund stem cell research in California.

That money has helped make California a global leader in stem cell research and led to ten clinical trials that the stem cell agency is funding this year alone. Those include trials in heart disease, cancer, leukemia, diabetes, blindness, HIV/AIDS and sickle cell disease.

To hear how that work has had an impact on the lives of patients we are holding a media briefing to look at the tremendous progress that has been made, and to hear what the future holds.

When: Thursday, November 20th at 11am

Where: Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at the University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033

Who: Hear from patients who have benefited from stem cell therapies, the researchers who have done the work, and the key figures in the drive to make California the global leader in stem cell research

To listen in to the event by phone:

Call in: 866.528.2256  Participant code: 1594399

For more information contact: Kevin McCormack, Communications Director, CIRM kmccormack@cirm.ca.gov

Cell: 415-361-2903

How venture capital became a capital adventure for stem cell agency’s newest Board member

Kathy LaPorte, the newest member of the CIRM Board

Kathy LaPorte, the newest member of the CIRM Board

There’s something fascinating about looking at the arc of a person’s career. So often we start out thinking we are going to be one thing, and over the years we move in a different direction and end up doing something else entirely.

That’s certainly the case with Kathy LaPorte, the newest addition to our governing Board, the Independent Citizens Oversight Committee (ICOC).

Ms. Laporte started out with dreams of being a doctor and, after getting a biology degree at Yale University, she applied to go to medical school at both Stanford and Harvard (she was accepted at both, which tells you something about her ability). But somewhere along the way she realized that being a doctor was not for her and so she started thinking about other directions. The one she ultimately chose was business.

And she went about it in style. After gaining experience with a number of firms she teamed up with some colleagues to start New Leaf Venture Partners, a venture capital firm based in Silicon Valley.

A profile of her in the Silicon Valley Business Journal described her as “smart, thorough and solution-oriented, Ms. LaPorte has spent nearly her entire professional life in venture capital — something of a rarity — and is considered a quick study by those who have worked with her.”

But it’s not just her business acumen that earned her the respect of colleagues and an appointment to our Board by State Treasurer Bill Lockyer. It’s also her experience working in the biotech and healthcare field, evaluating and mentoring later stage biotech companies and early stage medical device and diagnostic companies.

“I’m honored to be joining the Board, and excited about CIRM’s mission to bring new regenerative medicine therapies to patients with chronic diseases,” says Ms. LaPorte. “I hope my experience from 28 years of helping to finance and guide the work of passionate scientists and entrepreneurs, enabling their ideas to get to the people who really need them, will be helpful to the CIRM team.”

In a news release announcing the news, Jonathan Thomas, the Chair of our Board, said:

“We are thrilled to have Kathy join us on the ICOC. As a representative of a life science commercial entity she brings with her a wealth of knowledge and expertise in biotech and business development for healthcare companies and products. Her keen intellect and analytical skills are going to be terrific assets for the Board.”

Ms. LaPorte’s career took a few twists and turns before it led to us, but we’re delighted it brought her here, and we welcome her to the Board.

Hands-on science turns kids heads

Making science fun. That was the goal of the Discovery Days event on Saturday in San Francisco, part of the Bay Area Science Festival. If numbers alone are any measure of success they certainly met their goal. The place was packed. But it was more than just the size of the crowd that demonstrated how successful the event was; it was also the makeup and enthusiasm of those there.

Using Play-Doh to explain the wonders of stem cells

Using Play-Doh to explain the wonders of stem cells

For five hours on a beautiful, sunny Saturday – when they could have gone anywhere and done anything – tens of thousands of people, parents and children, chose to come to Discovery Days and immerse themselves in science. And they clearly loved it.

There were more than 150 exhibits to choose from with a wide variety of topics to learn about – everything from climate change and exploring outer space to life in the ocean and everything in between.

In just the small section where the stem cell agency had its booth there were exhibits on DNA and genetics, the power of imagination, and a program designed to encourage more young women to pursue careers in engineering and orthopedics.

Each one chose a different way to engage the crowd, some used fancy high tech tools, others chose more basic approaches. At our booth we used Play-Doh to draw children to us where they could learn about cellular development. It’s always fun to see their eyes widen in amazement when you show them how we all began: as a single, solitary cell. And how that single cell quickly divides into many, eventually making up all the different types of cells that make us human.

The stem cell agency booth at Discovery Days at AT&T Park

The stem cell agency booth at Discovery Days at AT&T Park

The enthusiasm by kids and parents alike was infectious—children racing from one booth to the next, eager to see what each one had in store. Of course the fact that some booths wowed the parents as well as the kids didn’t hurt—but the bottom line was the science and the scientists, showing that it could be fun and fascinating and engaging. While not many parents got into the Play-Doh themselves, they spent considerable time talking with us about the progress in stem cell science.

When you look around and see so many children wearing big goggles, pretending to be scientists, it’s not hard to think of them years later, wearing those same goggles and no longer pretending but actually working as researchers—truly making the world a better place.

And ultimately that was the goal of the event, helping the kids find “something that will unleash their inner scientist.”

CIRM 2.0; saving time, saves lives

It’s been almost ten years since the voters of California approved Proposition 71, creating the Stem Cell Agency and giving us $3 billion to fund stem cell research. So this is an appropriate time to look back and see what we have done with the money so far, the progress that’s been made, and where we are heading in the next ten years.

Over the next few weeks we’ll be taking a more detailed look at all these elements – it’s too much to cover in one blog – but let’s start with where we’re heading. At yesterday’s meeting of our governing Board, the Independent Citizens Oversight Committee, President & CEO, C. Randal Mills, Ph.D. charted a course for future funding.

Randy Mills, Stem Cell Agency President & CEO

Randy Mills, Stem Cell Agency President & CEO

Right now it can take up to two years for a project going into clinical trials to apply for and get funding from us. As Randy said in a news release we issued after the meeting, “That’s just unacceptable”:

Under what he is calling CIRM 2.0, Randy is proposing to trim that down dramatically:

“We are going to shorten that to just 120 days. But we’re not just making it faster, we’re also making it easier for companies or institutions with a therapy that is ready to go into clinical trials to be able to get funding for their project when they need it. Under this new system they will be able to apply anytime, and not have to try and shoehorn their needs into our application process.”

The goal is not just to make it easier to apply for funding, but also to get more, high quality applications. Right now there is pressure on companies to apply before they are really ready because they know if they miss a current application deadline it could be another year to 18 months before another award cycle comes around. Under CIRM 2.0 application will be accepted on a monthly basis, so applicants won’t have to worry about missing one deadline – they can just apply the following month. Applying when they are ready will increase the likelihood that the projects will be and of high quality.

And as Randy points out, if it works at the clinical stage of funding, it can work at every stage:

“Speeding up the process, at all stages of research, just makes sense. The faster that researchers can get access to the funds they need to do their work, the faster they are likely to be able to produce something that helps patients.”

The speeding up of the process doesn’t just involve companies and researchers being able to apply anytime, it also means that when they do apply they’ll have to have all the supporting documentation and studies on hand to show they are ready to go as soon as the Board approves funding.

In the past there was often a delay of six months or even more after an application had been approved for funding while research milestones were negotiated and agreements signed. Because CIRM 2.0 will involve identifying milestones much earlier in the application process that delay will disappear.

This new approach involves a complete overhaul of the way we currently work but we think it’s worth it. We plan to start by introducing these changes for the projects that are furthest along, those ready to go into clinical trials, but in time we intend extending this to cover everything we fund.

Making these changes will help us trim a two-year process down to just three months. That means any therapy that proves successful is getting to the patients who need it much sooner than it otherwise would. And with many of the diseases we are targeting, saving time means saving lives.