Stem cells could offer hope for deadly childhood muscle wasting disease

Duchenne muscular dystrophy (DMD) is a particularly nasty rare and fatal disease. It predominantly affects boys, slowly robbing them of their ability to control their muscles. By 10 years of age, boys with DMD start to lose the ability to walk; by 12, most need a wheelchair to get around. Eventually they become paralyzed, and need round-the-clock care.

There are no effective long-term treatments and the average life expectancy is just 25.

Crucial discovery

Duchenne MD team

DMD Research team: Photo courtesy Ottawa Hospital Research Inst.

But now researchers in Canada have made a discovery that could pave the way to new approaches to treating DMD. In a study published in the journal Nature Medicine, they show that DMD is caused by defective muscle stem cells.

In a news release Dr. Michael Rudnicki, senior author of the study, says this discovery is completely changing the way they think about the condition:

“For nearly 20 years, we’ve thought that the muscle weakness observed in patients with Duchenne muscular dystrophy is primarily due to problems in their muscle fibers, but our research shows that it is also due to intrinsic defects in the function of their muscle stem cells. This completely changes our understanding of Duchenne muscular dystrophy and could eventually lead to far more effective treatments.”

Loss and confused

DMD is caused by a genetic mutation that results in the loss of a protein called dystrophin. Rudnicki and his team found that without dystrophin muscle stem cells – which are responsible for repairing damage after injury – produce far fewer functional muscle fibers. The cells are also confused about where they are:

“Muscle stem cells that lack dystrophin cannot tell which way is up and which way is down. This is crucial because muscle stem cells need to sense their environment to decide whether to produce more stem cells or to form new muscle fibers. Without this information, muscle stem cells cannot divide properly and cannot properly repair damaged muscle.”

While the work was done in mice the researchers are confident it will also apply to humans, as the missing protein is almost identical in all animals.

Next steps

The researchers are already looking for ways they can use this discovery to develop new treatments for DMD, hopefully one day turning it from a fatal condition, to a chronic one.

Dr. Ronald Worton, the co-discoverer of the DMD gene in 1987, says this discovery has been a long-time coming but is both welcome and exciting:

“When we discovered the gene for Duchenne muscular dystrophy, there was great hope that we would be able to develop a new treatment fairly quickly. This has been much more difficult than we initially thought, but Dr. Rudnicki’s research is a major breakthrough that should renew hope for researchers, patients and families.”

In this video CIRM grantee, Dr. Helen Blau from Stanford University, talks about a new mouse model created by her lab that more accurately mimics the Duchenne symptoms observed in people. This opens up opportunities to better understand the disease and to develop new therapies.






The road to a cure for HIV/AIDS

Something wonderful sometimes happens when scientists and the public get together to talk about research. All the jargon, all the technical language falls away and it becomes instead a conversation between the two groups with most at stake, the people in need of a treatment or cure, and the people trying to develop it.

HIV Matters Town Hall, West Hollywood

HIV Matters Town Hall, West Hollywood

Last week CIRM joined with the AIDS Project Los Angeles to hold a Town Hall event in West Hollywood called HIV Matters: Countdown to a Cure: California Leads the Way. Around 120 people showed up to listen to stem cell scientists from City of Hope, University of Southern California (USC), Calimmune, and Sangamo Biosciences all of whom are using CIRM funding to develop new treatments, hopefully even cures, for HIV/AIDS.

Just a few years ago an event like this would have been unthinkable. The idea of talking about curing HIV/AIDS would have opened you up to ridicule and accusations of hyping the science. Today CIRM is funding three projects that have been approved for clinical trials (you can read about those here, here and here) and other research that is pushing the boundaries of our knowledge in search of even better approaches.

As David Hardy, the Chief Medical Officer for Calimmune, said:

“What is exciting today is that cure is now something that can be talked about as a potential reality.”

After brief presentations to discuss their work and the science behind it the panel opened the event up to questions from the audience.

Panel L to R: John Zaia, Dale Ando, David Hardy, Paula Cannon

Panel L to R: John Zaia, Dale Ando, David Hardy, Paula Cannon

One of the first questions silenced the room. “Is death a possible side effect of these clinical trials?”

Dr. John Zaia, the Chief of Virology at City of Hope near Los Angeles (and the lead investigator on one of the clinical trials) answered without any hesitation. “Yes”.

“We do everything we can to limit all side effects, especially the most extreme ones, but we have to be honest with patients and explain it is a remote possibility. That’s why it is covered in the informed consent process that every person goes through before signing up for the trial. We want to make sure everyone completely understands what they are signing up for.”

Dr. Dale Ando, Chief Medical Officer at Sangamo BioSciences, talked about the other approaches that are currently being explored to kill the AIDS virus, such as “shock and kill”, where a combination of drugs flushes the virus from hidden reservoirs in the body and then a boost to the immune system kills it.

Paula Cannon, PhD., a CIRM grantee and stem cell scientist at the Keck School of Medicine at USC, talked about her research aimed at developing the next generation of stem cell therapy targeting HIV/AIDS.

Current approaches take blood stem cells out of the body, genetically modify them so they are resistant to the virus, then return them to create a new blood and improved immune system. Cannon’s work is going to try and do that inside the body, without the need to remove the blood stem cells, in essence copying what the AIDS virus does when it infects cells and using that approach against it, creating a one-stop anti-viral approach to kill HIV.

It’s an audacious idea. But sometimes audacity is what you need to make big changes.

CIRM Board member and Patient Advocate for HIV/AIDS, Jeff Sheehy, moderated the discussion and ended the evening with a tribute to all the people who volunteered to be part of these, and every, clinical trial.

“They know, particularly in these early stage clinical trials where the focus is just showing that this approach is safe, that they are not likely to experience any benefit themselves. But they still volunteer, because they want to be part of something that could help many others. There’s a real sense of altruism. They want to advance the science.”

And the science is advancing. Maybe not always as fast as everyone would hope but we are making progress. And with each advance we get one step closer to our ultimate goal, of advancing stem cell therapies to patients with unmet medical needs.

CIRM Board meeting now underway – key votes expected on new CIRM 2.0 proposals and funding for disease research

The Board meeting is taking place at the Marriott in downtown Oakland. If you would like to hear the discussion there are a number of options:

Dial in Information:
Dial In Number: (866) 254-5938
Access Code: 365023

WebEx Link:
To join the event as an attendee
1. Go to…
2. Click “Join Now”

We will have a full report on the meeting in Friday’s blog

2,000 year old drug could fight breast cancer

Aspirin: a new option for breast cancer?

Aspirin: a new option for breast cancer?

Aspirin has been around about as long as anyone has been writing about health. Hippocrates, who was born in 460 BC and is frequently referred to as “The Father of Western Medicine”, used willow bark and leaves – which contain the active ingredients found in aspirin – to help ease pain and fevers. Now a new study says it may also be able to help people battling breast cancer.

A study in the journal Laboratory Investigation looked at the ability of acetylsalicylic acid (the chemical name for aspirin) to block the replication of cancer stem cells in breast cancer. Cancer stem cells are thought to be able to evade chemotherapy or other anti-cancer therapies and help the disease spread or metastasize throughout the body.

Sushanta Banerjee and his team at the Cancer Research Unit at the Kansas City (Mo.) Veterans Affairs Medical Center isolated breast cancer cells and then exposed half of them to varying doses of aspirin. The cells exposed to aspirin either stopped growing or died.

Working in the lab is one thing, working in animals can be something completely different, so the researchers next took 20 mice that had aggressive breast tumors. Half were given the human equivalent of a “low dose” aspirin, half received nothing. After 15 days the mice on aspirin had tumors that were almost half the size of the tumors on the non-treated mice.

But the researchers still weren’t done. They also wanted to see if aspirin could help prevent the spread of the cancer in the first place. So they worked with another group of mice: half got aspirin for ten days, the other half got nothing. The entire group was then exposed to cancer cells. After 15 days the mice on aspirin had considerably less cancer than the untreated group.

Banerjee talked about the significance of their findings in an article in Drug Discovery & Development:

“Our studies, for the first time, showed that aspirin can block the self-renewal capacity of breast cancer stem cells, and growth of breast tumor-initiating cells (BTICs)/breast cancer stem cells (BCSCs), which are also considered breast cancer residual cells, under tissue culture conditions. In addition, we found that aspirin-pre-exposed cells delay the formation of a palpable tumor in a xenograft mice model.  These studies suggest aspirin can prevent disease relapse, and enhance long-term survival of breast cancer patients.”

The article does discuss some of the limitations of the study – such as the dose involved, the length of follow-up and our ability to extrapolate the findings to people. And of course because of the risk of internal bleeding it’s not recommended that people just start taking aspirin without first consulting their own doctor.

Even so, Ricardo Fodde, Ph.D. an Erasmus Medical Center expert on the use of aspirin to treat cancer, says the findings are important:

“I find the general idea of using aspirin in a cancer therapeutic setting quite exciting.” Aspirin is “an extremely cheap and relatively innocuous—at least when compared with conventional cytotoxic drugs—non-steroid anti-inflammatory drug (NSAID) that possibly targets what is nowadays regarded as the beating heart of the tumor mass: cancer stem cells.”

Last November we wrote about a study showing aspirin might also be useful in fighting colon cancer. You can read about that work here.

Countdown to a cure for HIV/AIDS: California leads the way

shutterstock_98186870Not so long ago using the words ‘HIV/AIDS’ and ‘cure’ in the same sentence would have been considered inappropriate, even reckless. Although there were many antiretroviral medications that were effective at helping control the virus, there was nothing that was even remotely close to a cure on the horizon. And those therapies that had been approved were not always readily available, even in the U.S., let alone in the hardest hit countries in Africa.

Today the picture looks quite different. Cure is no longer just a distant dream, it’s a goal. CIRM has two projects that we are funding in clinical trials – one led by Calimmune Inc. and one by City of Hope and Sangamo BioSciences – whose ultimate goal is to replicate the experience of the “Berlin patient” and effectively cure people with the virus.

And we are not alone, the National Institute for Allergy and Infectious Diseases (NIAID) supports a large portfolio of investigator-initiated grants in HIV cure research, including programs to identify where HIV hides, known as the HIV reservoir, and to determine how these hideouts are established and maintained and then to get rid of them.

With this progress in mind we are partnering with the AIDS Project Los Angeles (APLA), Being Alive and the University of Southern California (USC) to host an HIV/AIDS Town Hall event called “Countdown to a Cure: California Leads the Way.”

The goal of the event is to bring together members of the HIV community and leading researchers in the field to talk about the clinical trials that are underway now, and the other approaches that are being tried to cure AIDS.

Speakers at the Town Hall are Dr. Paula Cannon, USC; Dr. David Hardy, Calimmune; Dr. John Zaia, City of Hope; and Dr. Dale Ando, Sangamo BioSciences. The conversation will be moderated by Jeff Sheehy. Jeff is not only the CIRM Board Patient Advocate member for HIV/AIDS, he’s also a long time community activist in the fight against the virus. You can hear Jeff talk about his commitment to the cause in this video.

The event is on Thursday, July 30th from 5.30p to 8.30p and we’re providing food and refreshments. The location is Fiesta Hall, Plummer Park, 7377 Santa Monica Boulevard, West Hollywood, Los Angeles. And, of course, it’s free.

If you are interested in joining us and being part of the discussion please RSVP to: or call 323-874-4322.

We look forward to seeing you there.

Using your own tumor to fight skin cancer

Some things never get old. Like watching the sunset over the Grand Canyon. Listening to a baby laugh. Watching the San Francisco Giants win the baseball World Series. Now you can add to that list learning that one of the clinical trials we are funding has just treated their first patient.

shutterstock_85468885The latest to join that growing list is Caladrius Biosciences (previously called NeoStem). We recently awarded them $17.7 million to carry out a Phase 3 metastatic melanoma clinical trial targeting cancer stem cells. These cells are believed to be able to survive chemotherapy and other cancer-targeting treatments, and can cause a relapse by enabling tumors to grow and spread.

Caladrius’ approach is a personalized one. They use the patient’s own tumor cells to create a therapeutic vaccine called (for now at least) CLBS20. It’s designed to engage the patient’s own immune system and destroy the cancer.

This first patient was treated at Thomas Jefferson University Hospital in Philadelphia. Altogether Caladrius hopes to enroll some 250 patients at more than 40 sites worldwide, for the trial. Seven of those sites are here in California; that’s the portion of the project we are funding.

Because this is a randomized, double blind study it’s not known if the patient was treated with CLBS20 or a placebo. But in a news release Dr. David J. Mazzo, CEO of Caladrius Biosciences, says it’s a big first step:

“The dosing of the first patient in this Phase 3 trial is an important milestone for our Company and the timing underscores our focus on this program and our commitment to impeccable trial execution. We are delighted by the enthusiasm and productivity of the team at Jefferson University and other trial sites around the country and look forward to translating that into optimized patient enrollment and a rapid completion of the Phase 3 trial.”

In the earlier Phase 2 trial, 72 percent of those who got the therapy were still alive after two years, compared to 31 percent of people who got a placebo therapy. There was another bonus for patients; the treatment was well-tolerated with few side effects, the most common being irritation and a reaction at the site of the injection.

There’s a big need for this approach. In 2014 there were approximately 20,000 new cases of metastatic melanoma and nearly 10,000 deaths. It usually causes death within one to two years and only 10 to 15 percent of patients survive five years.

Here’s where to go if you would like more information on the Intus Study or you can also visit the NIH clinical trials site.

Fate of our nerve stem cells determined early in embryo so the few we have as adults have very specific roles

Adult nerve stem cells fall in the category of allusive creatures. A few scientists still question their existence and most suggest they exist in small numbers only in one or two locations in the adult brain. In any case, all agree they are not particularly good at the normal function of stem cells—making repairs to their surrounding tissue.

A research team at the University of California, San Francisco, recently published results providing two reasons why adult nerve stem cells are not very robust. First they don’t self-renew—make more copies of themselves—on a regular basis.

While we have many types of nerves in our brains, our adult stem cells seem preprogrammed to form certain ones.

While we have many types of nerves in our brains, our adult stem cells seem preprogrammed to form certain ones.

Second, the ones you were born with were preprogrammed before birth to become only a narrow subset of the many nerves we need for a fully functioning brain.

Working in mice, the team led by Arturo Alvarez-Buylla found several types of stem cells on the walls of cavities in the brain and each was pre-programmed to be “progenitors” for a specific subset of nerves. Like progenitors appeared to be lumped together by location and the team also tracked the time during embryo development when these destiny designations are made.

These results could make folks reconsider how they might use adult nerve stem cells for therapy. Alvarez-Buylla explained in a UCSF press release picked up by ScienceNewsline:

“It may be unwelcome news for those who thought of adult neural stem cells as having a wide potential for neural repair. Instead, it looks as if that potential is narrowed down very early during embryonic development. It’s almost as if the embryo is planning for the future.”

He went on to argue that the study points out the critical importance of understanding how stem cells develop and change in the embryo because that knowledge will guide how we use the various stem cells in therapy.

CIRM did not fund this study, but we do fund work in the Alvarez-Buylla lab that seeks to create nerve cells that can be implanted into people with diseases like epilepsy that result from an imbalance between different types of nerves.

Help us chart a new direction

It’s hard to get where you want to go without a map. Even if you have a pretty good idea of where you are heading it’s all too easy to get sidetracked or take a wrong turn. Having a good map helps you stay on course.

Charting a course for success

Charting a course for success

That’s why we are creating our own map, to help us reach our goal, of accelerating stem cell therapies to patients with unmet medical needs.

We’re putting together a new Strategic Plan, something that will help shape our future as we head into our second decade. The idea is simple, how can we best use the money we have left (almost one billion dollars) and all our other resources.

To do that we’re asking the usual suspects for their thoughts and ideas, but we’re also asking some unusual suspects, in fact, we’re asking anyone who is interested to help us develop the plan.

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

“No one has a monopoly on good ideas, that’s why we want to hear from a diverse group of people, scientists and non-scientists alike, to learn what they think about how we should best use our money, resources, and expertise to reach our goal. This new Strategic Plan will help create a clear vision for how we move forward, one that sets priorities and an actionable approach to accomplish our mission.”

Anyone wishing to add their voice to those helping us develop the plan can take the online anonymous survey. The deadline is the end of the day Friday, June 26th.


As the Chair of our governing Board, Jonathan Thomas, Ph.D., J.D., says:

“We are a state agency. We were created by the people of California and we answer to the people of California. It makes sense that for something this important, a Strategic Plan that will help shape our future for years to come, that we ask the people of California for their thoughts and suggestions.”

Science is filled with uncertainty. Even the most promising therapeutic approach can take a wrong turn. Having a clear road map, a well thought out Strategic Plan, is no guarantee of success, but it certainly means we’ll have a much better idea of how to get where we want to go.

New stem cell could unlock key to colon cancer

One of the fascinating things about stem cell research is how quickly the field is evolving. It seems like every other day a new study is published that highlights a new discovery that makes us stop and think how this new knowledge affects our understanding of stem cells and the diseases we are trying to treat.

The latest example came this week with research from Canada identifying a new kind of stem cell population found in the colon that can lead to cancer growth.

shutterstock_280962560The study, published in the journal Cell Stem Cell,  is important because colon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer death in both men and women, claiming around 50,000 lives in the U.S. alone every year.

Stem cells are essential for helping replace the lining of our colon and intestine every three or four days. In the intestine there are two kinds of stem cells, a rapidly recycling one called Lgr5+ and a slower one. However, scientists had only been able to identify Lgr5+ stem cells in the colon. Because this stem cell type is sensitive to radiation physicians believed that radiation therapy would be effective against colon cancer.

Now, researchers at Lawson Health Research Institute in Ontario, Canada, have identified another stem cell in the colon, one that is both long-lived and radiation resistant.

They also found that this new stem cell population can not only give rise to tumors in the colon, it can also help sustain and support the growth of the cancer.

In a news release Dr. Samuel Asfaha, a clinician-scientist at Lawson and the lead author of the study, says this new piece of information gives them vital new information in fighting the cancer:

 “The identification of more than one stem cell pool in the colon has proven challenging. These findings are exciting, as we have identified an important new target for cancer therapy. It is also proof that more than one stem cell can give rise to and sustain tumors, telling us that our cancer therapy needs to target more than one stem cell pool.”

Asfaha says knowing that there is a pool of stem cells that don’t respond to radiation means researchers must now look for new, more effective ways of tackling them, so we are better able to help patients with colon cancer.

CIRM is funding a number of therapies that target solid tumor cancers, the kind that includes colon cancer. One, run by Dr. Dennis Slamon of University College, Los Angeles, is now in clinical trials. You can read about that work here.

Neat trick grows two parts of the brain and gets them to communicate

Over the past year or so, teams around the world have reported using stem cells to make increasingly complex portions of the brain. Earlier this month we wrote about a team at Stanford who had grown “organoids” that simulated the brain’s cortex with both nerves and support cells that communicated back and forth with each other. Now, a team at the National Institutes of Health has created nerves from two distinct parts of the brain and got them to make connections for the cross-talk that makes our brains so wonderfully complex.

Cortex nerves (green) and mDA nerves (red) shown connecting with fine tendrils.

Cortex nerves (green) and mDA nerves (red) shown connecting with fine tendrils.

The researchers used reprogrammed iPS type stem cells made from skin samples to create two types of nerves in two separate chambers of a lab container. One, called mesencephalic dopaminergic (mDA) nerves, has been linked to disorders like drug abuse, schizophrenia and attention deficit-hyperactivity disorder. In the other chamber they grew nerves that became part of the brain’s cortex responsible for memory, attention and language.

After coaxing the stem cells to become the two distinct nerve types in their own chamber, the researchers removed a barrier between the chambers and observed the two cell types making the kind of connections needed for thought.

The lead researcher, Chun-Ting Lee described the value of this new system in understanding disease using human pluripotent stem cells (hPSCs), either iPS or embryonic:

“This method, therefore, has the potential to expand the potential of hPSC-derived neurons to allow for studies of human neural systems and interconnections that have previously not been possible to model in vitro.”

A press release from the journal Restorative Neurology and Neuroscience was picked up by ScienceNewsline.