From bench to bedside: a Q&A with stem cell expert Jan Nolta

At CIRM we are privileged to work with many remarkable people who combine brilliance, compassion and commitment to their search for new therapies to help people in need. One of those who certainly fits that description is UC Davis’ Jan Nolta.

This week the UC Davis Newsroom posted a great interview with Jan. Rather than try and summarize what she says I thought it would be better to let her talk for herself.

Jan Nolta
Jan Nolta

Talking research, unscrupulous clinics, and sustaining the momentum

(SACRAMENTO) —

In 2007, Jan Nolta returned to Northern California from St. Louis to lead what was at the time UC Davis’ brand-new stem cell program. As director of the UC Davis Stem Cell Program and the Institute for Regenerative Cures, she has overseen the opening of the institute, more than $140 million in research grants, and dozens upon dozens of research studies. She recently sat down to answer some questions about regenerative medicine and all the work taking place at UC Davis Health.

Q: Turning stem cells into cures has been your mission and mantra since you founded the program. Can you give us some examples of the most promising research?

I am so excited about our research. We have about 20 different disease-focused teams. That includes physicians, nurses, health care staff, researchers and faculty members, all working to go from the laboratory bench to patient’s bedside with therapies.

Perhaps the most promising and exciting research right now comes from combining blood-forming

stem cells with gene therapy. We’re working in about eight areas right now, and the first cure, something that we definitely can call a stem cell “cure,” is coming from this combined approach.

Soon, doctors will be able to prescribe this type of stem cell therapy. Patients will use their own bone marrow or umbilical cord stem cells. Teams such as ours, working in good manufacturing practice facilities, will make vectors, essentially “biological delivery vehicles,” carrying a good copy of the broken gene. They will be reinserted into a patient’s cells and then infused back into the patient, much like a bone marrow transplant.

“Perhaps the most promising and exciting research right now comes from combining blood-forming stem cells with gene therapy.”

Along with treating the famous bubble baby disease, where I had started my career, this approach looks very promising for sickle cell anemia. We’re hoping to use it to treat several different inherited metabolic diseases. These are conditions characterized by an abnormal build-up of toxic materials in the body’s cells. They interfere with organ and brain function. It’s caused by just a single enzyme. Using the combined stem cell gene therapy, we can effectively put a good copy of the gene for that enzyme back into a patient’s bone marrow stem cells. Then we do a bone marrow transplantation and bring back a person’s normal functioning cells.

The beauty of this therapy is that it can work for the lifetime of a patient. All of the blood cells circulating in a person’s system would be repaired. It’s the number one stem cell cure happening right now. Plus, it’s a therapy that won’t be rejected. These are a patient’s own stem cells. It is just one type of stem cell, and the first that’s being commercialized to change cells throughout the body.

Q: Let’s step back for a moment. In 2004, voters approved Proposition 71. It has funded a majority of the stem cell research here at UC Davis and throughout California. What’s been the impact of that ballot measure and how is it benefiting patients?

We have learned so much about different types of stem cells, and which stem cell will be most appropriate to treat each type of disease. That’s huge. We had to first do that before being able to start actual stem cell therapies. CIRM [California Institute for Regenerative Medicine] has funded Alpha Stem Cell Clinics. We have one of them here at UC Davis and there are only five in the entire state. These are clinics where the patients can go for high-quality clinical stem cell trials approved by the FDA [U.S. Food and Drug Administration]. They don’t need to go to “unapproved clinics” and spend a lot of money. And they actually shouldn’t.

“By the end of this year, we’ll have 50 clinical trials.”

By the end of this year, we’ll have 50 clinical trials [here at UC Davis Health]. There are that many in the works.

Our Alpha Clinic is right next to the hospital. It’s where we’ll be delivering a lot of the immunotherapies, gene therapies and other treatments. In fact, I might even get to personally deliver stem cells to the operating room for a patient. It will be for a clinical trial involving people who have broken their hip. It’s exciting because it feels full circle, from working in the laboratory to bringing stem cells right to the patient’s bedside.

We have ongoing clinical trials for critical limb ischemia, leukemia and, as I mentioned, sickle cell disease. Our disease teams are conducting stem cell clinical trials targeting sarcoma, cellular carcinoma, and treatments for dysphasia [a swallowing disorder], retinopathy [eye condition], Duchenne muscular dystrophy and HIV. It’s all in the works here at UC Davis Health.

There’s also great potential for therapies to help with renal disease and kidney transplants. The latter is really exciting because it’s like a mini bone marrow transplant. A kidney recipient would also get some blood-forming stem cells from the kidney donor so that they can better accept the organ and not reject it. It’s a type of stem cell therapy that could help address the burden of being on a lifelong regime of immunosuppressant drugs after transplantation.

Q: You and your colleagues get calls from family members and patients all the time. They frequently ask about stem cell “miracle” cures. What should people know about unproven treatments and unregulated stem cell clinics?

That’s a great question.The number one rule is that if you’re asked to pay money for a stem cell treatment, don’t do it. It’s a big red flag.

When it comes to advertised therapies: “The number one rule is that if you’re asked to pay money for a stem cell treatment, don’t do it. It’s a big red flag.”

Unfortunately, there are unscrupulous people out there in “unapproved clinics” who prey on desperate people. What they are delivering are probably not even stem cells. They might inject you with your own fat cells, which contain very few stem cells. Or they might use treatments that are not matched to the patient and will be immediately rejected. That’s dangerous. The FDA is shutting these unregulated clinics down one at a time. But it’s like “whack-a-mole”: shut one down and another one pops right up.

On the other hand, the Alpha Clinic is part of our mission is to help the public get to the right therapy, treatment or clinical trial. The big difference between those who make patients pay huge sums of money for unregulated and unproven treatments and UC Davis is that we’re actually using stem cells. We produce them in rigorously regulated cleanroom facilities. They are certified to contain at least 99% stem cells.

Patients and family members can always call us here. We can refer them to a genuine and approved clinical trial. If you don’t get stem cells at the beginning [of the clinical trial] because you’re part of the placebo group, you can get them later. So it’s not risky. The placebo is just saline. I know people are very, very desperate. But there are no miracle cures…yet. Clinical trials, approved by the FDA, are the only way we’re going to develop effective treatments and cures.

Q: Scientific breakthroughs take a lot of patience and time. How do you and your colleagues measure progress and stay motivated?   

Motivation?  “It’s all for the patients.”

It’s all for the patients. There are not good therapies yet for many disorders. But we’re developing them. Every day brings a triumph. Measuring progress means treating a patient in a clinical trial, or developing something in the laboratory, or getting FDA approval. The big one will be getting biological license approval from the FDA, which means a doctor can prescribe a stem cell or gene therapy treatment. Then it can be covered by a patient’s health insurance.

I’m a cancer survivor myself, and I’m also a heart patient. Our amazing team here at UC Davis has kept me alive and in great health. So I understand it from both sides. I understand the desperation of “Where do I go?” and “What do I do right now?” questions. I also understand the science side of things. Progress can feel very, very slow. But everything we do here at the Institute for Regenerative Cures is done with patients in mind, and safety.

We know that each day is so important when you’re watching a loved one suffer. We attend patient events and are part of things like Facebook groups, where people really pour their hearts out. We say to ourselves, “Okay, we must work harder and faster.” That’s our motivation: It’s all the patients and families that we’re going to help who keep us working hard.

Blood-brain barrier chip created with stem cells expands potential for personalized medicine

An Organ-Chip used in the study to create a blood-brain barrier (BBB).

The brain is a complex part of the human body that allows for the formation of thoughts and consciousness. In many ways it is the essence of who we are as individuals. Because of its importance, our bodies have developed various layers of protection around this vital organ, one of which is called the blood-brain barrier (BBB).

The BBB is a thin border of various cell types around the brain that regulate what can enter the brain tissue through the bloodstream. Its primary purpose is to prevent toxins and other unwanted substances from entering the brain and damaging it. Unfortunately this barrier can also prevent helpful medications, designed to fix problems, from reaching the brain.

Several brain disorders, such as Amyotrophic Lateral Sclerosis (ALS – also known as Lou Gehrig’s disease), Parkinson’s Disease (PD), and Huntington’s Disease (HD) have been linked to defective BBBs that keep out critical biomolecules needed for healthy brain activity.

In a CIRM-funded study, a team at Cedars-Sinai Medical Center created a BBB through the use of stem cells and an Organ-Chip made from induced pluripotent stem cells (iPSCs). These are a specific type of stem cells that can turn into any type of cell in the body and can be generated from a person’s own cells. In this study, iPSCs were created from adult blood samples and used to make the neurons and other supporting cells that make up the BBB. These cells were then placed inside an Organ-Chip which recreates the environment that cells normally experience within the human body.

Inside the 3-D Organ-Chip, the cells were able to form a BBB that functions as it does in the body, with the ability to block entry of certain drugs. Most notably, when the BBB was generated from cell samples of patients with HD, the BBB malfunctioned in the same way that it does in patients with the disease.

These findings expand the potential for personalized medicine for various brain disorders linked to problems in the BBB. In a press release, Dr. Clive Svendsen, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and senior author of the study, was quoted as saying,

“The study’s findings open a promising pathway for precision medicine. The possibility of using a patient-specific, multicellular model of a blood barrier on a chip represents a new standard for developing predictive, personalized medicine.”

The full results of the study were published in the scientific journal Cell Stem Cell.

Advancing stem cell research in many ways

Speakers at the Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

From Day One CIRM’s goal has been to advance stem cell research in California. We don’t do that just by funding the most promising research -though the 51 clinical trials we have funded to date clearly shows we do that rather well – but also by trying to bring the best minds in the field together to overcome problems.

Over the years we have held conferences, workshops and symposiums on everything from Parkinson’s disease, cerebral palsy and tissue engineering. Each one attracted the key players and stakeholders in the field, brainstorming ideas to get past obstacles and to explore new ways of developing therapies. It’s an attempt to get scientists, who would normally be rivals or competitors, to collaborate and partner together in finding the best way forward.

It’s not easy to do, and the results are not always obvious right away, but it is essential if we hope to live up to our mission of accelerating stem cell therapies to patients with unmet medical needs.

For example. This past week we helped organize two big events and were participants in another.

The first event we pulled together, in partnership with Cedars-Sinai Medical Center, was a workshop called “Brainstorm Neurodegeneration”. It brought together leaders in stem cell research, genomics, big data, patient advocacy and the Food and Drug Administration (FDA) to tackle some of the issues that have hampered progress in finding treatments for things like Parkinson’s, Alzheimer’s, ALS and Huntington’s disease.

We rather ambitiously subtitled the workshop “a cutting-edge meeting to disrupt the field” and while the two days of discussions didn’t resolve all the problems facing us it did produce some fascinating ideas and some tantalizing glimpses at ways to advance the field.

Alpha Stem Cell Clinics Network Symposium: Photo by Marco Sanchez

Two days later we partnered with UC San Francisco to host the Fourth Annual CIRM Alpha Stem Cell Clinics Network Symposium. This brought together the scientists who develop therapies, the doctors and nurses who deliver them, and the patients who are in need of them. The theme was “The Past, Present & Future of Regenerative Medicine” and included both a look at the initial discoveries in gene therapy that led us to where we are now as well as a look to the future when cellular therapies, we believe, will become a routine option for patients. 

Bringing these different groups together is important for us. We feel each has a key role to play in moving these projects and out of the lab and into clinical trials and that it is only by working together that they can succeed in producing the treatments and cures patients so desperately need.

Cierra Jackson: Photo by Marco Sanchez

As always it was the patients who surprised us. One, Cierra Danielle Jackson, talked about what it was like to be cured of her sickle cell disease. I think it’s fair to say that most in the audience expected Cierra to talk about her delight at no longer having the crippling and life-threatening condition. And she did. But she also talked about how hard it was adjusting to this new reality.

Cierra said sickle cell disease had been a part of her life for all her life, it shaped her daily life and her relationships with her family and many others. So, to suddenly have that no longer be a part of her caused a kind of identity crisis. Who was she now that she was no longer someone with sickle cell disease?

She talked about how people with most diseases were normal before they got sick, and will be normal after they are cured. But for people with sickle cell, being sick is all they have known. That was their normal. And now they have to adjust to a new normal.

It was a powerful reminder to everyone that in developing new treatments we have to consider the whole person, their psychological and emotional sides as well as the physical.

CIRM’s Dr. Maria Millan (right) at a panel presentation at the Stanford Drug Discovery Symposium. Panel from left to right are: James Doroshow, NCI; Sandy Weill, former CEO Citigroup; Allan Jones, CEO Allen Institute

And so on to the third event we were part of, the Stanford Drug Discovery Symposium. This was a high level, invitation-only scientific meeting that included some heavy hitters – such as Nobel Prize winners Paul Berg and  Randy Schekman, former FDA Commissioner Robert Califf. Over the course of two days they examined the role that philanthropy plays in advancing research, the increasingly important role of immunotherapy in battling diseases like cancer and how tools such as artificial intelligence and big data are shaping the future.

CIRM’s President and CEO, Dr. Maria Millan, was one of those invited to speak and she talked about how California’s investment in stem cell research is delivering Something Better than Hope – which by a happy coincidence is the title of our 2018 Annual Report. She highlighted some of the 51 clinical trials we have funded, and the lives that have been changed and saved by this research.

The presentations at these conferences and workshops are important, but so too are the conversations that happen outside the auditorium, over lunch or at coffee. Many great collaborations have happened when scientists get a chance to share ideas, or when researchers talk to patients about their ideas for a successful clinical trial.

It’s amazing what happens when you bring people together who might otherwise never have met. The ideas they come up with can change the world.

Rare Disease Gets Big Boost from California’s Stem Cell Agency

UC Irvine’s Dr. Leslie Thompson and patient advocate Frances Saldana after the CIRM Board vote to approve funding for Huntington’s disease

If you were looking for a poster child for an unmet medical need Huntington’s disease (HD) would be high on the list. It’s a devastating disease that attacks the brain, steadily destroying the ability to control body movement and speech. It impairs thinking and often leads to dementia. It’s always fatal and there are no treatments that can stop or reverse the course of the disease. Today the Board of the California Institute for Regenerative Medicine (CIRM) voted to support a project that shows promise in changing that.

The Board voted to approve $6 million to enable Dr. Leslie Thompson and her team at the University of California, Irvine to do the late stage testing needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people. The therapy involves transplanting stem cells that have been turned into neural stem cells which secrete a molecule called brain-derived neurotrophic factor (BDNF), which has been shown to promote the growth and improve the function of brain cells. The goal is to slow down the progression of this debilitating disease.

“Huntington’s disease affects around 30,000 people in the US and children born to parents with HD have a 50/50 chance of getting the disease themselves,” says Dr. Maria T. Millan, the President and CEO of CIRM. “We have supported Dr. Thompson’s work for a number of years, reflecting our commitment to helping the best science advance, and are hopeful today’s vote will take it a crucial step closer to a clinical trial.”

Another project supported by CIRM at an earlier stage of research was also given funding for a clinical trial.

The Board approved almost $12 million to support a clinical trial to help people undergoing a kidney transplant. Right now, there are around 100,000 people in the US waiting to get a kidney transplant. Even those fortunate enough to get one face a lifetime on immunosuppressive drugs to stop the body rejecting the new organ, drugs that increase the risk for infection, heart disease and diabetes.  

Dr. Everett Meyer, and his team at Stanford University, will use a combination of healthy donor stem cells and the patient’s own regulatory T cells (Tregs), to train the patient’s immune system to accept the transplanted kidney and eliminate the need for immunosuppressive drugs.

The initial group targeted in this clinical trial are people with what are called HLA-mismatched kidneys. This is where the donor and recipient do not share the same human leukocyte antigens (HLAs), proteins located on the surface of immune cells and other cells in the body. Around 50 percent of patients with HLA-mismatched transplants experience rejection of the organ.

In his application Dr. Meyer said they have a simple goal: “The goal is “one kidney for life” off drugs with safety for all patients. The overall health status of patients off immunosuppressive drugs will improve due to reduction in side effects associated with these drugs, and due to reduced graft loss afforded by tolerance induction that will prevent chronic rejection.”

Midwest universities are making important tools to advance stem cell research

580b4-ipscell

iPSCs are not just pretty, they’re also pretty remarkable

Two Midwest universities are making headlines for their contributions to stem cell research. Both are developing important tools to advance this field of study, but in two unique ways.

Scientists at the University of Michigan (UM), have compiled an impressive repository of disease-specific stem cell lines. Cell lines are crucial tools for scientists to study the mechanics of different diseases and allows them to do so without animal models. While animal models have important benefits, such as the ability to study a disease within the context of a living mammal, insights gained from such models can be difficult to translate to humans and many diseases do not even have good models to use.

The stem cell lines generated at the Reproductive Sciences Program at UM, are thanks to numerous individuals who donated extra embryos they did not use for in vitro fertilization (IVF). Researchers at UM then screened these embryos for abnormalities associated with different types of disease and generated some 36 different stem cell lines. These have been donated to the National Institute of Health’s (NIH) Human Embryonic Stem Cell Registry, and include cell lines for diseases such as cystic fibrosis, Huntington’s Disease and hemophilia.

Using one such cell line, Dr. Peter Todd at UM, found that the genetic abnormality associated with Fragile X Syndrome, a genetic mutation that results in developmental delays and learning disabilities, can be corrected by using a novel biological tool. Because Fragile X Syndrome does not have a good animal model, this stem cell line was critical for improving our understanding of this disease.

In the next state over, at the University of Wisconsin-Madison (UWM), researchers are doing similar work but using induced pluripotent stem cells (iPSCs) for their work.

The Human Stem Cell Gene Editing Service has proved to be an important resource in expediting research projects across campus. They use CRISPR-Cas9 technology (an efficient method to mutate or edit the DNA of any organism), to generate human stem cell lines that contain disease specific mutations. Researchers use these cell lines to determine how the mutation affects cells and/or how to correct the cellular abnormality the mutation causes. Unlike the work at UM, these stem cell lines are derived from iPSCs  which can be generated from easy to obtain human samples, such as skin cells.

The gene editing services at UWM have already proved to be so popular in their short existence that they are considering expanding to be able to accommodate off-campus requests. This highlights the extent to which both CRISPR technology and stem cell research are being used to answer important scientific questions to advance our understanding of disease.

CIRM also created an iPSC bank that researchers can use to study different diseases. The  Induced Pluripotent Stem Cell (iPSC) Repository is  the largest repository of its kind in the world and is used by researchers across the globe.

The iPSC Repository was created by CIRM to house a collection of stem cells from thousands of individuals, some healthy, but some with diseases such as heart, lung or liver disease, or disorders such as autism. The goal is for scientists to use these cells to better understand diseases and develop and test new therapies to combat them. This provides an unprecedented opportunity to study the cell types from patients that are affected in disease, but for which cells cannot otherwise be easily obtained in large quantities.

Meet the high school student who moonlights as a neuroscientist

As part of our CIRM scholar blog series, we’re featuring the research and career accomplishments of CIRM funded students. Today, you’ll read about one of our former SPARK high school students.


Emma Friedenberg and former CIRM SPARK Director Karen Ring at the 2017 SPARK Conference.

Emma Friedenberg is a high school senior at Campbell Hall in North Hollywood, California. She’s also an up-and-coming neuroscientist who has her sights set on unraveling the complexities of the brain and discovering cures for degenerative brain diseases. Emma spent the summer of 2017 studying Huntington’s disease in the lab of Dr. Virginia Mattis at the Cedars-Sinai Medical Center. Her internship was possible because of the CIRM SPARK high school educational program which gives California students the opportunity to do stem cell research for a summer.

Below is an interview with Emma about her SPARK experience and how the program is helping her pursue her passions for research and medicine.

Q: How did you learn about the CIRM SPARK program and why did you want to apply?

I’ve been a clinical volunteer at Cedars-Sinai Medical Center for two years in the Intensive Care Unit and the Neurology and Spine Unit. I was submitting my application to return as a volunteer when I explored Cedars-Sinai’s Outreach website page and found the CIRM SPARK program. I knew immediately it was a perfect fit. I plan on studying neuroscience in college with an intention of obtaining my medical degree and becoming a surgeon. The CIRM SPARK program at Cedars within the Board of Governor’s Regenerative Medicine Institute had an option to be involved specifically in the Brain Program. In Dr. Virginia Mattis’ lab, I studied translational stem cell therapies for neurodegenerative diseases, in particular Huntington’s Disease. As Cedars-Sinai calls it, a “bench to bedside” approach is an unparalleled and invaluable experience and huge advantage in science.

Q: What was your SPARK research project?

At Cedars-Sinai, I was mentored by Dr. Virginia Mattis in her stem cell lab. The Mattis Lab researches stem cell therapies for Huntington’s disease (HD), a neurodegenerative brain disease. HD is caused by a loss of neurons, specifically medium spiny neurons in the striatum of Huntington’s patients. We used induced pluripotent stem cells to model HD in a petri dish to study the development of the disease and to create medium spiny neurons that could one day be transplanted into Huntington’s patients to replace lost and damaged cells.

Medium spiny neurons made from Huntington’s disease patient induced pluripotent stem cells. (Image credit: Mattis Lab, Cedars Sinai)

My primary research in the Mattis Lab was experimenting on our cell line to find the most time and cost-effective procedure to produce large populations of medium spiny neurons, because current methods are expensive and largely inefficient. However, my internship was not limited to the laboratory. I spent a significant amount of time shadowing doctors in the ALS Clinic.

Q: What was your experience in the CIRM SPARK program like?

In one word, the CIRM SPARK program was incredible –a one of a kind opportunity. The sciences are my personal passion and the cornerstone of my academic pursuits. The CIRM SPARK program has bolstered my scientific knowledge and provided practical experience in a real-world laboratory environment. A career in medicine is a significant commitment, and I’m confident the CIRM SPARK program was a beneficial start to obtaining my goals.

Cedars-Sinai SPARK students celebrating the completion of their 2017 internships.

Q: What do you value most about your SPARK experience?

It was wonderful to be part of a program which understood collaboration and offered a plethora of learning opportunities outside of the wet lab. What I will keep with me is not only techniques of immunocytochemistry and microscopy, but also the advice and encouragement from accomplished scientists like Clive Svendsen and my mentor Virginia Mattis.

Q: What are your future goals?

I plan on studying neuroscience in college with an intention of obtaining my medical degree and becoming a surgeon.

Q: Who is your scientific idol and why?

I recently read Dr. Eric Kandel’s book, The Age of Insight: The Quest to Understand the Unconscious in Art, Mind, and Brain, from Vienna 1900 to the Present. Dr. Kandel is a neuroscientist and a Professor at Columbia University. He received the Nobel Prize for his work in memory storage using Aplysia, a type of sea slug. His book examines how the human brain responds to art. What I find so inspiring about his book is his interdisciplinary approach to science, a combination of neuroscience, psychoanalysis, biology, and art. The human brain is so complicated that it can be studied from numerous perspectives, from biology to chemistry to electrophysiology. It is not until we can begin to merge these understandings that we will begin to unlock the secrets of the brain. Dr. Kandel is not only a scientist, but an intellectual.

Q: What is your favorite thing about being a scientist?

For centuries, the human brain was an anomaly, unexplainable by science. With 100 billion neurons and 100 trillion connections, the brain is the most complex network in the universe. How the brain functions as an information-processing organ and regulates emotion, behavior, and cognition as well as basic body functions like breathing remains a mystery. In recent years, there has been significant progress in brain research. Scientists are on the brink of major breakthroughs, but there is significant work to do particularly on neurological brain disorders. Being a scientist means living on the cutting-edge of human innovation. I enjoy being able to both ask and answer questions that will benefit humankind.


Related Links:

Stem Cell Roundup: New understanding of Huntington’s; how stem cells can double your DNA; and using “the Gary Oldman of cell types” to reverse aging

This week’s roundup highlights how we are constantly finding out new and exciting ways that stem cells could help change the way we treat disease.

Our Cool Stem Cell Image of the Week comes from our first story, about unlocking some of the secrets of Huntington’s disease. It comes from the Laboratory of Stem Cell Biology and Molecular Embryology at The Rockefeller University

Huntington's neurons

A new approach to studying and developing therapies for Huntington’s disease

Researchers at Rockefeller University report new findings that may upend the way scientists study and ultimately develop therapies for Huntington’s disease, a devastating, inherited neurodegenerative disorder that has no cure. Though mouse models of the disease are well-established, the team wanted to focus on human biology since our brains are more complex than those of mice. So, they used CRISPR gene editing technology in human embryonic stem cells to introduce the genetic mutations that cause HD.

Though symptoms typically do not appear until adulthood, the researchers were surprised to find that in their human cell-based model of HD, abnormalities in nerve cells occur at the earliest steps in brain development. These results suggest that HD therapies should focus on treatments much earlier in life.

The researchers observed another unexpected twist: cells that lack Huntingtin, the gene responsible for HD, are very similar to cells found in HD. This suggests that too little Huntingtin may be causing the disease. Up until now, the prevailing idea has been that Huntington’s symptoms are caused by the toxicity of too much mutant Huntingtin activity.

We’ll certainly be keeping an eye on how further studies using this new model affect our understanding of and therapy development for HD.

This study was published in Development and was picked by Science Daily.

How you can double your DNA

dna

As you can imagine we get lots of questions about stem cell research here at CIRM. Last week we got an email asking if a stem cell transplant could alter your DNA? The answer is, under certain circumstances, yes it could.

A fascinating article in the Herald Review explains how this can happen. In a bone marrow transplant bad blood stem cells are killed and replaced with healthy ones from a donor. As those cells multiply, creating a new blood supply, they also carry the DNA for the donor.

But that’s not the only way that people may end up with dual DNA. And the really fascinating part of the article is how this can cause all sorts of legal and criminal problems.

One researcher’s efforts to reverse aging

gary-oldman

Gary Oldman: Photo courtesy Variety

“Stem cells are the Gary Oldman of cell types.” As a fan of Gary Oldman (terrific as Winston Churchill in the movie “Darkest Hour”) that one line made me want to read on in a profile of Stanford University researcher Vittorio Sebastiano.

Sebastiano’s goal is, to say the least, rather ambitious. He wants to reverse aging in people. He believes that if you can induce a person’s stem cells to revert to a younger state, without changing their function, you can effectively turn back the clock.

Sebastiano says if you want to achieve big things you have to think big:

“Yes, the ambition is huge, the potential applications could be dramatic, but that doesn’t mean that we are going to become immortal in some problematic way. After all, one way or the other, we have to die. We will just understand aging in a better way, and develop better drugs, and keep people happier and healthier for a few more years.”

The profile is in the journal Nautilus.

Treatments, cures and clinical trials: an in-person update on CIRM’s progress

Patients and Patient Advocates are at the heart of everything we do at CIRM. That’s why we are holding three free public events in the next few months focused on updating you on the stem cell research we are funding, and our plans for the future.

Right now we have 33 projects that we have funded in clinical trials. Those range from heart disease and stroke, to cancer, diabetes, ALS (Lou Gehrig’s disease), two different forms of vision loss, spinal cord injury and HIV/AIDS. We have also helped cure dozens of children battling deadly immune disorders. But as far as we are concerned we are only just getting started.

Over the course of the next few years, we have a goal of adding dozens more clinical trials to that list, and creating a pipeline of promising therapies for a wide range of diseases and disorders.

That’s why we are holding these free public events – something we try and do every year. We want to let you know what we are doing, what we are funding, how that research is progressing, and to get your thoughts on how we can improve, what else we can do to help meet the needs of the Patient Advocate community. Your voice is important in helping shape everything we do.

The first event is at the Gladstone Institutes in San Francisco on Wednesday, September 6th from noon till 1pm. The doors open at 11am for registration and a light lunch.

Gladstone Institutes

Here’s a link to an Eventbrite page that has all the information about the event, including how you can RSVP to let us know you are coming.

We are fortunate to be joined by two great scientists, and speakers – as well as being CIRM grantees-  from the Gladstone Institutes, Dr. Deepak Srivastava and Dr. Steve Finkbeiner.

Dr. Srivastava is working on regenerating heart muscle after it has been damaged. This research could not only help people recover from a heart attack, but the same principles might also enable us to regenerate other organs damaged by disease. Dr. Finkbeiner is a pioneer in diseases of the brain and has done ground breaking work in both Alzheimer’s and Huntington’s disease.

We have two other free public events coming up in October. The first is at UC Davis in Sacramento on October 10th (noon till 1pm) and the second at Cedars-Sinai in Los Angeles on October 30th (noon till 1pm). We will have more details on these events in the coming weeks.

We look forward to seeing you at one of these events and please feel free to share this information with anyone you think might be interested in attending.

Advocating for Huntington’s Disease: Daniel Medina’s Journey

Daniel Medina

In honor of Huntington’s Disease (HD) Awareness Month, we’re featuring a guest blog by HD patient advocate Daniel Medina. Daniel became actively involved in the HD community when he learned that his younger brother was at risk for inheriting this devastating neurodegenerative disease. Since then he has been a champion for HD awareness by organizing HD patient support groups and walks in southern California and serving on the Board of HD Care, UC Irvine’s non-profit HD support group. 


Guest Blog by Daniel Medina

A visit to a care home back in April of 2012 changed my life forever. It all started when my mother took my 14-year-old half-brother to meet his grandfather for the very first time. My brother’s aunt led the way to what seemed to be an emotional, long overdue family encounter.  As they walked into his room they were impacted by what they saw.

They saw an elderly, bedridden gentleman that suffered from uncontrollable body movements. He was unable to communicate and was totally dependent on others. As the tears flowed, so did my mom’s sense of urgency to find out the name of his affliction. That’s when the words “Huntington’s disease” were uttered by my brother’s aunt. Her knowledge was limited to sharing that it was a genetic disease.

I immediately began my own research as the details of this encounter were relayed to me. My curiosity soon turned into despair and anguish as I learned that my brother was at risk of being a carrier of this horrible neurodegenerative disease.  I felt empowered as I began attending HD fundraising events. There I met so many courageous families that clung to the hope of a better tomorrow.  This hope came through the possibility of scientists working towards finding a treatment or a cure through stem cell research.

As of 2013 my role had evolved from an event attendee to a patient advocate. It became clear to me that there was an immediate need to fill voids that were unattended. In 2014, I started an HD support group in my area in order to tend to the needs of the HD community. The appreciation and gratitude I felt made every second I invested very much worthwhile.

In the last three years, we have seen the tremendous impact and growth HD organizations like Help4HD International, HD CARE and WeHaveAFace, have had on a local and global scale. It has been such an honor and a privilege to work alongside them. Our collaborative efforts have had a ripple effect of amazing results. The success of one is the success of all.

At the beginning of 2015, I was introduced to Americans for Cures. Working to promote and educate the public about the benefits of stem cell stem research was a perfect fit. Meeting advocates from other disease communities has educated me and taught me how our common goals towards finding cures unites us.

My HD Advocacy journey began with a simple visit to a care home. In a matter of a few years, it has transformed into a life mission to help those suffering the effects of this terrible disease.

2016 HD-CARE Conference. Patient Advocates Ron Shapiro, Adrienne Shapiro, David Saldana, Frances Saldana, Daniel Medina with Karen Ring from CIRM.

Stem cell-derived blood-brain barrier gives more complete picture of Huntington’s disease

Like a sophisticated security fence, our bodies have evolved a barrier that protects the brain from potentially harmful substances in the blood but still allows the entry of essential molecules like blood sugar and oxygen. Just like in other parts of the body, the blood vessels and capillaries in the brain are lined with endothelial cells. But in the brain, these cells form extremely tight connections with each other making it nearly impossible for most things to passively squeeze through the blood vessel wall and into the brain fluid.

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Compared to blood vessels in other parts of the body, brain blood vessels form a much tighter seal to protect the brain.
Image source: Dana and Chris Reeve Foundation

Recent studies have shown defects in the brain-blood barrier are associated with neurodegenerative disorders like Huntington’s disease and as a result becomes leakier. Although the debilitating symptoms of Huntington’s disease – which include involuntary movements, severe mood swings and difficulty swallowing – are primarily due to the gradual death of specific nerve cells, this breakdown in the blood-brain barrier most likely contributes to the deterioration of the Huntington’s brain.

What hasn’t been clear is if mutations in Huntingtin, the gene that is linked to Huntington’s disease, directly impact the specialized endothelial cells within the blood-brain barrier or if these specialized cells are just innocent bystanders of the destruction that occurs as Huntington’s progresses. It’s an important question to answer. If the mutations in Huntingtin directly affect the blood-brain barrier then it could provide a bigger picture of how this incurable, fatal disease works. More importantly, it may provide new avenues for therapy development.

A UC Irvine research team got to the bottom of this question with the help of induced pluripotent stem cells (iPSCs) derived from the skin cells of individuals with Huntington’s disease. Their CIRM-funded study was published this week in Cell Reports.

In a first for a neurodegenerative disease, the researchers coaxed the Huntington’s disease iPSCs in a lab dish to become brain microvascular endothelial cells (BMECs), the specialized cells responsible for forming the blood-brain barrier. The researchers found that the Huntington’s BMECs themselves were indeed dysfunctional. Compared to BMECs derived from unaffected individuals, the Huntington’s BMECs weren’t as good at making new blood vessels, and the vessels they did make were leakier. So the Huntingtin mutation in these BMECs appears to be directly responsible for the faulty blood-brain barrier.

The team dug deeper into this new insight by looking for possible differences in gene activity between the healthy and Huntington’s BMECs. They found that the Wnt group of genes, which plays an important role in the development of the blood-brain barrier, are over active in the Huntington’s BMECs. This altered Wnt activity can explain the leaky defects. In fact, the use of a drug inhibitor of Wnt fixed the defects. Dr. Leslie Thompson, the team lead, described the significance of this finding in a press release:

“Now we know there are internal problems with blood vessels in the brain. This discovery can be used for possible future treatments to seal the leaky blood vessels themselves and to evaluate drug delivery to patients with HD.”

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Study leader, Leslie Thompson. Steve Zylius / UCI

A companion Cell Stem Cell report, also published this week, used the same iPSC-derived blood-brain barrier system. In that study, researchers at Cedars-Sinai pinpointed BMEC defects as the underlying cause of Allan-Herndon-Dudley syndrome, another neurologic condition that causes mental deficits and movement problems. Together these results really drive home the importance of studying the blood-brain barrier function in neurodegenerative disease.

Dr. Ryan Lim, the first author on the UC Irvine study, also points to a larger perspective on the implications of this work:

“These studies together demonstrate the incredible power of iPSCs to help us more fully understand human disease and identify the underlying causes of cellular processes that are altered.”