Stem cell treatment restores man’s sight in right eye after 25 years

James O’Brien, recipient of a stem cell treatment that restored the vision in his right eye

At 18 years old, there are several life-changing moments that young people look forward to. For some, it involves graduating from high school, starting college, and being able to cast a vote in an election. For others, this momentous occasion symbolizes the official start of adulthood.

For James O’ Brien, this milestone was marked by a rather unfortunate event where ammonia was thrown at his face in a random attack. As a result of this incident, the surface of his right eye was burned and he was left completely blind in his right eye.

Fast forward 25 years and thanks to an experimental stem cell treatment, James is able to see out of his right eye for the first time since the attack.

“Being able to see with both eyes – it’s a small thing that means the world. Basically I went from near-blindness in that eye to being able to see everything.” said O’Brien in a news release from Daily Heralds.

Dr. Sajjad Ahmad and a team of surgeons at the Moorfields Eye Hospital in London removed healthy stem cells from O’Brien’s left eye and grew these cells in a lab for months. After an adequate number of healthy stem cells from O’Briens left eye were grown, the surgeons then cut the scar tissue in his right eye and replaced it with the healthy stem cells.

They then waited a year after the procedure for the cells to settle down before inserting a cornea – which plays a key role in vision and focuses light – from a deceased donor.

“This is going to have a huge impact. A lot of these patients are young men so it affects their work, their lives, those around them. It’s not just the vision that drops, it’s the pain.” said Dr. Ahmad in the news release previously mentioned.

The procedure used took over 20 years to develop and Dr. Ahmad hopes to continue to develop the procedure for patients that have been blinded in both eyes by chemicals or have lost their vision through degenerative conditions.

CIRM has funded three clinical trials in vision loss to date. Two of these trials are being conducted by Dr. Henry Klassen for an eye condition known as retinitis pigmentosa and have shown promising results. The third trial is being conducted by Dr. Mark Humayun for another eye condition known as age-related macular degeneration (AMD) which has also shown promising results.

See video below for a news segment of James O’Brien on BBC News:

Time and money and advancing stem cell research

The human genome

Way back in the 1990’s scientists were hard at work decoding the human genome, trying to map and understand all the genes that make up people. At the time there was a sense of hope, a feeling that once we had decoded the genome, we’d have cures for all sorts of things by next Thursday. It didn’t quite turn out that way.

The same was true for stem cell research. In the early days there was a strong feeling that this was going to quite quickly produce new treatments and cures for diseases ranging from Parkinson’s and Alzheimer’s to heart disease and stroke. Although we have made tremendous strides we are still not where we hoped we’d be.

It’s a tough lesson to learn, but an important one: good scientific research moves at its own pace and pays little heed to our hopes or desires. It takes time, often a long time, and money, usually a lot of money, to develop new treatments for deadly diseases and disorders.

Many people, particularly those battling deadly diseases who are running out of time, are frustrated at the slow pace of stem cell research, at the years and years of work that it takes to get even the most promising therapy into a clinical trial where it can be tested in people. That’s understandable. If your life is on the line, it’s difficult to be told that you have to be patient. Time is a luxury many patients don’t have.

But that caution is necessary. The last thing we want to do is rush to test something in people that isn’t ready. And stem cells are a whole new way of treating disease, using cells that may stay in the body for years, so we really need to be sure we have done everything we can to ensure they are safe before delivering them to people.

The field of gene therapy was set back years after one young patient, Jesse Gelsinger, died as a result of an early experimental treatment. We don’t want the same to happen to stem cell research.

And yet progress is being made, albeit not as quickly as any of us would like. At the end of the first ten years of CIRM’s existence we had ten projects that we supported that were either in, or applying to be in, a clinical trial sanctioned by the US Food and Drug Administration (FDA). Five years later that number is 56.

Most of those are in Phase 1 or 2 clinical trials which means they are still trying to show they are both safe and effective enough to be made available to a wider group of people. However, some of our projects are in Phase 3, the last step before, hopefully, being given FDA approval to be made more widely available and – just as important – to be covered by insurance.

Other CIRM-funded projects have been given Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA, a new program that allows projects that show they are safe and benefit patients in early stage clinical trials, to apply for priority review, meaning they could get approved faster than normal. Out of 40 RMAT designations awarded so far, six are for CIRM projects.

We are working hard to live up to our mission statement of accelerating stem cell treatments to patients with unmet medical needs. We have been fortunate in having $3 billion to spend on advancing this research in California; an amount no other US state, indeed few other countries, have been able to match. Yet even that amount is tiny compared to the impact that many of these diseases have. For example, the economic cost of treating diabetes in the US is a staggering $327 billion a year.

The simple truth is that unless we, as a nation, invest much more in scientific research, we are not going to be able to develop cures and new, more effective, treatments for a wide range of diseases.

Time and money are always going to be challenging when it comes to advancing stem cell research and bringing treatments to patients. With greater knowledge and understanding of stem cells and how best to use them we can speed up the timeline. But without money none of that can happen.

Our blog is just one of many covering the topic of “What are the hurdles impacting patient access to cell and gene therapies as part of Signal’s fourth annual blog carnival.

Stem cell progress and promise in fighting leukemia

Computer illustration of a cancerous white blood cell in leukemia.

There is nothing you can do to prevent or reduce your risk of leukemia. That’s not a very reassuring statement considering that this year alone almost 62,000 Americans will be diagnosed with leukemia; almost 23,000 will die from the disease. That’s why CIRM is funding four clinical trials targeting leukemia, hoping to develop new approaches to treat, and even cure it.

That’s also why our next special Facebook Live “Ask the Stem Cell Team” event is focused on this issue. Join us on Thursday, August 29th from 1pm to 2pm PDT to hear a discussion about the progress in, and promise of, stem cell research for leukemia.

We have two great panelists joining us:

Dr. Crystal Mackall, has many titles including serving as the Founding Director of the Stanford Center for Cancer Cell Therapy.  She is using an innovative approach called a Chimeric Antigen Receptor (CAR) T Cell Therapy. This works by isolating a patient’s own T cells (a type of immune cell) and then genetically engineering them to recognize a protein on the surface of cancer cells, triggering their destruction. This is now being tested in a clinical trial funded by CIRM.

Natasha Fooman. To describe Natasha as a patient advocate would not do justice to her experience and expertise in fighting blood cancer and advocating on behalf of those battling the disease. For her work she has twice been named “Woman of the Year” by the Leukemia and Lymphoma Society. In 2011 she was diagnosed with a form of lymphoma that was affecting her brain. Over the years, she would battle lymphoma three times and undergo chemotherapy, radiation and eventually a bone marrow transplant. Today she is cancer free and is a key part of a CIRM team fighting blood cancer.

We hope you’ll join us to learn about the progress being made using stem cells to combat blood cancers, the challenges ahead but also the promising signs that we are advancing the field.

We also hope you’ll take an active role by posting questions on Facebook during the event, or sending us questions ahead of time to info@cirm.ca.gov. We will do our best to address as many as we can.

Here’s the link to the event, feel free to share this with anyone you think might be interested in joining us for Facebook Live “Ask the Stem Cell Team about Leukemia”

One family’s fight to save their son’s life, and how stem cells made it possible

CIRM’s mission is very simple: to accelerate stem cell treatments to patients with unmet medical needs. Anne Klein’s son, Everett, was a poster boy for that statement. Born with a fatal immune disorder Everett faced a bleak future. But Anne and husband Brian were not about to give up. The following story is one Anne wrote for Parents magazine. It’s testament to the power of stem cells to save lives, but even more importantly to the power of love and the determination of a family to save their son.

My Son Was Born With ‘Bubble Boy’ Disease—But A Gene Therapy Trial Saved His Life

Everett Schmitt. Photo: Meg Kumin

I wish more than anything that my son Everett had not been born with severe combined immunodeficiency (SCID). But I know he is actually one of the lucky unlucky ones. By Anne Klein

As a child in the ’80s, I watched a news story about David Vetter. David was known as “the boy in the bubble” because he was born with severe combined immunodeficiency (SCID), a rare genetic disease that leaves babies with very little or no immune system. To protect him, David lived his entire life in a plastic bubble that kept him separated from a world filled with germs and illnesses that would have taken his life—likely before his first birthday.

I was struck by David’s story. It was heartbreaking and seemed so otherworldly. What would it be like to spend your childhood in an isolation chamber with family, doctors, reporters, and the world looking in on you? I found it devastating that an experimental bone marrow transplant didn’t end up saving his life; instead it led to fatal complications. His mother, Carol Ann Demaret, touched his bare hand for the first and last time when he was 12 years old.

I couldn’t have known that almost 30 years later, my own son, Everett, would be born with SCID too.

Everett’s SCID diagnosis

At birth, Everett was big, beautiful, and looked perfectly healthy. My husband Brian and I already had a 2-and-a-half-year-old son, Alden, so we were less anxious as parents when we brought Everett home. I didn’t run errands with Alden until he was at least a month old, but Everett was out and about with us within a few days of being born. After all, we thought we knew what to expect.

But two weeks after Everett’s birth, a doctor called to discuss Everett’s newborn screening test results. I listened in disbelief as he explained that Everett’s blood sample indicated he may have an immune deficiency.

“He may need a bone marrow transplant,” the doctor told me.

I was shocked. Everett’s checkup with his pediatrician just two days earlier went swimmingly. I hung up and held on to the doctor’s assurance that there was a 40 percent chance Everett’s test result was a false positive.

After five grueling days of waiting for additional test results and answers, I received the call: Everett had virtually no immune system. He needed to be quickly admitted to UCSF Benioff Children’s Hospital in California so they could keep him isolated and prepare to give him a stem cell transplant. UCSF diagnosed him specifically with SCID-X1, the same form David battled.

Beginning SCID treatment

The hospital was 90 miles and more than two hours away from home. Our family of four had to be split into two, with me staying in the hospital primarily with Everett and Brian and Alden remaining at home, except for short visits. The sudden upheaval left Alden confused, shaken, and sad. Brian and I quickly transformed into helicopter parents, neurotically focused on every imaginable contact with germs, even the mildest of which could be life-threatening to Everett.

When he was 7 weeks old, Everett received a stem cell transplant with me as his donor, but the transplant failed because my immune cells began attacking his body. Over his short life, Everett has also spent more than six months collectively in the hospital and more than three years in semi-isolation at home. He’s endured countless biopsies, ultrasounds, CT scans, infusions, blood draws, trips to the emergency department, and medical transports via ambulance or helicopter.

Gene therapy to treat SCID

At age 2, his liver almost failed and a case of pneumonia required breathing support with sedation. That’s when a doctor came into the pediatric intensive care unit and said, “When Everett gets through this, we need to do something else for him.” He recommended a gene therapy clinical trial at the National Institutes of Health (NIH) that was finally showing success in patients over age 2 whose transplants had failed. This was the first group of SCID-X1 patients to receive gene therapy using a lentiviral vector combined with a light dose of chemotherapy.

After the complications from our son’s initial stem cell transplant, Brian and I didn’t want to do another stem cell transplant using donor cells. My donor cells were at war with his body and cells from another donor could do the same. Also, the odds of Everett having a suitable donor on the bone marrow registry were extremely small since he didn’t have one as a newborn. At the NIH, he would receive a transplant with his own, perfectly matched, gene-corrected cells. They would be right at home.

Other treatment options would likely only partially restore his immunity and require him to receive infusions of donor antibodies for life, as was the case with his first transplant. Prior gene therapy trials produced similarly incomplete results and several participants developed leukemia. The NIH trial was the first one showing promise in fully restoring immunity, without a risk of cancer. Brian and I felt it was Everett’s best option. Without hesitation, we flew across the country for his treatment. Everett received the gene therapy in September 2016 when he was 3, becoming the youngest patient NIH’s clinical trial has treated.

Everett’s recovery

It’s been more than two years since Everett received gene therapy and now more than ever, he has the best hope of developing a fully functioning immune system. He just received his first vaccine to test his ability to mount a response. Now 6 years old, he’s completed kindergarten and has been to Disney World. He plays in the dirt and loves shows and movies from the ’80s (maybe some of the same ones David enjoyed).

Everett knows he has been through a lot and that his doctors “fixed his DNA,” but he’s focused largely on other things. He’s vocal when confronted with medical pain or trauma, but seems to block out the experiences shortly afterwards. It’s sad for Brian and me that Everett developed these coping skills at such a young age, but we’re so grateful he is otherwise expressive and enjoys engaging with others. Once in the middle of the night, he woke us up as he stood in the hallway, exclaiming, “I’m going back to bed, but I just want you to know that I love you with all my heart!”

I wish more than anything that Everett had not been born with such a terrible disease and I could erase all the trauma, isolation, and pain. But I know that he is actually one of the lucky unlucky ones. Everett is fortunate his disease was caught early by SCID newborn screening, which became available in California not long before his birth. Without this test, we would not have known he had SCID until he became dangerously ill. His prognosis would have been much worse, even under the care of his truly brilliant and remarkable doctors, some of whom cared for David decades earlier.

Carol-Ann-mother-of-David-Vetter-meeting-Everett-Schmitt
Everett Schmitt meeting David Vetter’s mom Carol Ann Demaret. Photo – Brian Schmitt

When Everett was 4, soon after the gene therapy gave him the immunity he desperately needed, our family was fortunate enough to cross paths with David’s mom, Carol Ann, at an Immune Deficiency Foundation event. Throughout my life, I had seen her in pictures and on television with David. In person, she was warm, gracious, and humble. When I introduced her to Everett and explained that he had SCID just like David, she looked at Everett with loving eyes and asked if she could touch him. As she touched Everett’s shoulder and they locked eyes, Brian and I looked on with profound gratitude.

Anne Klein is a parent, scientist, and a patient advocate for two gene therapy trials funded by the California Institute for Regenerative Medicine. She is passionate about helping parents of children with SCID navigate treatment options for their child.

You can read about the clinical trials we are funding for SCID here, here, here and here.

CIRM Board Approves New Clinical Trial for Breast Cancer Related Brain Metastases

Dr. Saul Priceman

Yesterday the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $9.28 million to Dr. Saul Priceman at City of Hope to conduct a clinical trial for the treatment of breast cancer related brain metastases, which are tumors in the brain that have spread from the original site of the breast cancer.

This award brings the total number of CIRM-funded clinical trials to 56. 

Breast cancer is the second-most common cancer in women, both in the United States (US) and worldwide.  It is estimated that over 260,000 women in the US will be diagnosed with breast cancer in 2019 and 1 out of 8 women in the US will get breast cancer at some point during her lifetime. Some types of breast cancer have a high likelihood of metastasizing to the brain.  When that happens, there are few treatment options, leading to a poor prognosis and poor quality of life. 

Dr. Priceman’s clinical trial is testing a therapy to treat brain metastases that came from breast cancers expressing high levels of a protein called HER2.   The therapy consists of a genetically-modified version of the patient’s own T cells, which are an immune system cell that can destroy foreign or abnormal cells.  The T cells are modified with a protein called a chimeric antigen receptor (CAR) that recognizes the tumor protein HER2.  These modified T cells (CAR-T cells) are then infused into the patient’s brain where they are expected to detect and destroy the HER2-expressing tumors in the brain.

CIRM has also funded the earlier work related to this study, which was critical in preparing the therapy for Food and Drug Administration (FDA) approval for permission to start a clinical trial in people.

“When a patient is told that their cancer has metastasized to other areas of the body, it can be devastating news,” says Maria T. Millan, M.D., the President and CEO of CIRM.  “There are few options for patients with breast cancer brain metastases.  Standard of care treatments, which include brain irradiation and chemotherapy, have associated neurotoxicity and do little to improve survival, which is typically no more than a few months.  CAR-T cell therapy is an exciting and promising approach that now offers us a more targeted approach to address this condition.”

The CIRM Board also approved investing $19.7 million in four awards in the Translational Research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.

Dr. Mark Tuszynski at the University of California San Diego (UCSD) was awarded $6.23 million to develop a therapy for spinal cord injury (SCI). Dr. Tuszynski will use human embryonic stem cells (hESCs) to create neural stem cells (NSCs) which will then be grafted at the injury site.  In preclinical studies, the NSCs have been shown to help create a kind of relay at the injury site, restoring communication between the brain and spinal cord and re-establishing muscle control and movement.

Dr. Mark Humayun at the University of Southern California (USC) was awarded $3.73 million to develop a novel therapeutic product capable of slowing the progression of age-related macular degeneration (AMD), the leading cause of vision loss in the US.

The approach that Dr. Humayun is developing will use a biologic product produced by human embryonic stem cells (hESCs). This material will be injected into the eye of patients with early development of dry AMD, supporting the survival of photoreceptors in the affected retina, the kind of cells damaged by the disease.

The TRAN1 awards went to:

Stay tuned for our next blog which will dive into each of these awards in much more detail.

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.

Developing a non-toxic approach to bone-crushing cancers

When cancer spreads to the bone the results can be devastating

Battling cancer is always a balancing act. The methods we use – surgery, chemotherapy and radiation – can help remove the tumors but they often come at a price to the patient. In cases where the cancer has spread to the bone the treatments have a limited impact on the disease, but their toxicity can cause devastating problems for the patient. Now, in a CIRM-supported study, researchers at UC Irvine (UCI) have developed a method they say may be able to change that.

Bone metastasis – where cancer starts in one part of the body, say the breast, but spreads to the bones – is one of the most common complications of cancer. It can often result in severe pain, increased risk of fractures and compression of the spine. Tackling them is difficult because some cancer cells can alter the environment around bone, accelerating the destruction of healthy bone cells, and that in turn creates growth factors that stimulate the growth of the cancer. It is a vicious cycle where one problem fuels the other.

Now researchers at UCI have developed a method where they combine engineered mesenchymal stem cells (taken from the bone marrow) with targeting agents. These act like a drug delivery device, offloading different agents that simultaneously attack the cancer but protect the bone.

Weian Zhao; photo courtesy UC Irvine

In a news release Weian Zhao, lead author of the study, said:

“What’s powerful about this strategy is that we deliver a combination of both anti-tumor and anti-bone resorption agents so we can effectively block the vicious circle between cancers and their bone niche. This is a safe and almost nontoxic treatment compared to chemotherapy, which often leaves patients with lifelong issues.”

The research, published in the journal EBioMedicine, has already been shown to be effective in mice. Next, they hope to be able to do the safety tests to enable them to apply to the Food and Drug Administration for permission to test it in people.

The team say if this approach proves effective it might also be used to help treat other bone-related diseases such as osteoporosis and multiple myeloma.

Regulated, reputable, and reliable – distinguishing legitimate clinical trials from predatory clinics

Here at CIRM, we get calls every day from patients asking us if there are any trials or therapies available to treat their illness or an illness affecting a loved one. Unfortunately, there are some predatory clinics that try to take advantage of this desperation by advertising unproven and unregulated treatments for a wide range of diseases such as Diabetes, Alzheimer’s, Parkinson’s, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS).

A recent article in the Los Angeles Times describes how one of these predatory stem cell clinics is in a class action lawsuit related to false advertising of 100% patient satisfaction. Patients were led to believe that this percentage was related to the effectiveness of the treatment, when in fact it had to do with satisfaction related to hospitality, hotel stay, and customer service. These kinds of deceptive tactics are commonplace for sham clinics and are used to convince people to pay tens of thousands of dollars for sham treatments.

But how can a patient or loved one distinguish a legitimate clinical trial or treatment from those being offered by predatory clinics? We have established the “fundamental three R’s” to help in making this distinction.

REGULATED

The United States Food and Drug Administration (FDA) has a regulated process that it uses in evaluating potential treatments from researchers seeking approval to test these in a clinical trial setting.  This includes extensive reviews by scientific peers in the community that are well informed on specific disease areas. Those that adhere to these regulations get an FDA seal of approval and are subject to extensive oversight to protect patients participating in this trial. Additionally, these regulations ensure that the potential treatments are properly evaluated for effectiveness. The 55 clinical trials that we have currently funded as well as the clinical trials being conducted in our Alpha Stem Cell Clinic Network all have this FDA seal of approval. In contrast to this, the treatments offered at predatory clinics have not gone through the rigorous standards necessary to obtain FDA approval.

REPUTABLE

We have partnered with reputable institutions to carry out the clinical trials we have funded and establish our Alpha Stem Cell Clinic Network. These are institutions that adhere to the highest scientific standards necessary to effectively evaluate potential treatments and communicate these results with extreme accuracy. These institutions have expert scientists, doctors, and nurses in the field and adhere to rigorous standards that have earned these institutions a positive reputation for carrying out their work.  The sites for the Alpha Stem Cell Clinic Network include City of Hope, UCSF, UC San Diego, UCLA, UC Davis, and UC Irvine.  In regards to the clinical trials we have directly funded, we have collaborated with other prestigious institutions such as Stanford and USC.  All these institutions have a reputation for being respected by established societies and other professionals in the field. The reputation that predatory clinics have garnered from patients, scientists, and established doctors has been a negative one. An article published in The New York Times has described the tactics used by these predatory clinics as unethical and their therapies have often been shown to be ineffective.

RELIABLE

The clinical trials we fund and those offered at our Alpha Stem Cell Clinic Network are reliable because they are trusted by patients, patient advocacy groups, and other experts in the field of regenerative medicine. A part of being reliable involves having extensive expertise and training to properly evaluate and administer treatments in a clinical trial setting. The doctors, nurses, and other experts involved in clinical trials given the go-ahead by the FDA have extensive training to carry out these trials.  These credentialed specialists are able to administer high quality clinical care to patients.  In a sharp contrast to this, an article published in Reuters showed that predatory clinics not only administer unapproved stem cell treatments to patients, but they use doctors that have not received training related to the services they provide.

Whenever you are looking at a potential clinical trial or treatment for yourself or a loved one, just remember the 3 R’s we have laid out in this blog.

Regulated, reputable, and reliable.

Breaking bad news to stem cell researchers

It’s never easy to tell someone that they are too late, that they missed the deadline. It’s particularly hard when you know that the person you are telling that to has spent years working on a project and now needs money to take it to the next level. But in science, as in life, it’s always better to tell people what they need to know rather than what they would like to hear.

And so, we have posted a notice on our website for researchers thinking about applying for funding that, except in a very few cases, they are too late, that there is no money available for new projects, whether it’s Discovery, Translational or Clinical.

Here’s that notice:

CIRM anticipates that the budget allocation of funds for new awards under the CIRM clinical program (CLIN1, CLIN2 and CLIN3) may be depleted within the next two to three months. CIRM will accept applications for the monthly deadline on June 28, 2019 but will suspend application submissions after that date until further notice. All applicants should note that the review of submitted applications may be halted at any point in the process if funds are depleted prior to completion of the 3-month review cycle. CIRM will notify applicants of such an occurrence. Therefore, submission and acceptance of an application to CIRM does not guarantee the availability of funds or completion of a review cycle.

The submission of applications for the CIRM/NHLBI Cure Sickle Cell Initiative (CLIN1 SCD, CLIN2 SCD) are unaffected and application submissions for this program will remain open.

We do, of course, have enough money set aside to continue funding all the projects our Board has already approved, but we don’t have money for new projects (except for some sickle cell disease projects).

In truth our funding has lasted a lot longer than anyone anticipated. When Proposition 71 was approved the plan was to give CIRM $300 million a year for ten years. That was back in 2004. So what happened?

Well, in the early years stem cell science was still very much in its infancy with most of the work being done at a basic or Discovery level. Those typically don’t require very large sums so we were able to fund many projects without hitting our $300m target. As the field progressed, however, more and more projects were at the clinical trial stage and those need multiple millions of dollars to be completed. So, the money went out faster.

To date we have funded 55 clinical trials and our early support has helped more than a dozen other projects get into clinical trials. This includes everything from cancer and stroke, to vision loss and diabetes. It’s a good start, but we feel there is so much more to do.

Followers of news about CIRM know there is talk about a possible ballot initiative next year that would provide another $5.5 billion in funding for us to help complete the mission we have started.

Over the years we have built a pipeline of promising projects and without continued support many of those projects face a difficult future. Funding at the federal level is under threat and without CIRM there will be a limited number of funding alternatives for them to turn to.

Telling researchers we don’t have any money to support their work is hard. Telling patients we don’t have any money to support work that could lead to new treatments for them, that’s hardest of all.

“A new awakening”: One patient advocate’s fight for her daughters life

We often talk about the important role that patient advocates play in helping advance research. That was demonstrated in a powerful way last week when the CIRM Board approved almost $12 million to fund a clinical trial targeting a rare childhood disorder called cystinosis.

The award, to Stephanie Cherqui and her team at UC San Diego (in collaboration with UCLA) was based on the scientific merits of the program. But without the help of the cystinosis patient advocate community that would never have happened. Years ago the community held a series of fundraisers, bake sales etc., and used the money to help Dr. Cherqui get her research started.

That money enabled Dr. Cherqui to get the data she needed to apply to CIRM for funding to do more detailed research, which led to her award last week. There to celebrate the moment was Nancy Stack. Her testimony to the Board was a moving celebration of how long they have worked to get to this moment, and how much hope this research is giving them.

Nancy Stack is pictured in spring 2018 with her daughter Natalie Stack and husband Geoffrey Stack. (Lar Wanberg/Cystinosis Research Foundation)

Hello my name is Nancy Stack and I am the founder and president of the Cystinosis Research Foundation.  Our daughter Natalie was diagnosed with cystinosis when she was an infant. 

Cystinosis is a rare disease that is characterized by the abnormal accumulation of cystine in every cell in the body.  The build-up of cystine eventually destroys every organ in the body including the kidneys, eyes, liver, muscles, thyroid and brain.  The average age of death from cystinosis and its complications is 28 years of age.

For our children and adults with cystinosis, there are no healthy days. They take between 8-12 medications around the clock every day just to stay alive – Natalie takes 45 pills a day.  It is a relentless and devastating disease.

Medical complications abound and our children’s lives are filled with a myriad of symptoms and treatments – there are g-tube feedings, kidney transplants, bone pain, daily vomiting,  swallowing difficulties, muscle wasting, severe gastrointestinal side effects and for some blindness.   

We started the Foundation in 2003.  We have worked with and funded Dr. Stephanie Cherqui since 2006.   As a foundation, our resources are limited but we were able to fund the initial grants for Stephanie’s  Stem Cell studies. When CIRM awarded a grant to Stephanie in 2016, it allowed her to complete the studies, file the IND and as a result, we now have FDA approval for the clinical trial. Your support has changed the course of this disease. 

When the FDA approved the clinical trial for cystinosis last year, our community was filled with a renewed sense of hope and optimism.  I heard from 32 adults with cystinosis – all of them interested in the clinical trial.  Our adults know that this is their only chance to live a full life. Without this treatment, they will die from cystinosis.  In every email I received, there was a message of hope and gratitude. 

I received an email from a young woman who said this, “It’s a new awakening to learn this morning that human clinical trials have been approved by the FDA. I reiterate my immense interest to participate in this trial as soon as possible because my quality of life is at a low ebb and the trial is really my only hope. Time is running out”. 

And a mom of a 19 year old young man who wants to be the first patient in the trial wrote and said this, “On the day the trial was announced I started to cry tears of pure happiness and I thought, a mother somewhere gets to wake up and have a child who will no longer have cystinosis. I felt so happy for whom ever that mom would be….I never imagined that the mom I was thinking about could be me. I am so humbled to have this opportunity for my son to try to live disease free.

My own daughter ran into my arms that day and we cried tears of joy – finally, the hope we had clung to was now a reality. We had come full circle.  I asked Natalie how it felt to know that she could be cured and she said, “I have spent my entire life thinking that I would die from cystinosis in my 30s but now, I might live a full life and I am thinking about how much that changes how I think about my future. I never planned too far ahead but now I can”. 

As a mother, words can’t possible convey what it feels like to know that my child has a chance to live a long, healthy life free of cystinosis – I can breathe again. On behalf of all the children and adults with cystinosis, thank you for funding Dr. Cherqui, for caring about our community, for valuing our children and for making this treatment a reality.  Our community is ready to start this trial – thank you for making this happen.

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CIRM will be celebrating the role of patient advocates at a free event in Los Angeles tomorrow. It’s at the LA Convention Center and here are the details. And did I mention it’s FREE!

Tue, June 25, 2019 – 6:00 PM – 7:00 PM PDT

Petree Hall C., Los Angeles Convention Center, 1201 South Figueroa Street Los Angeles, CA 90015

And on Wednesday, USC is holding an event highlighting the progress being made in fighting diseases that destroy vision. Here’s a link to information about the event.