State Stem Cell & Gene Therapy Agency Sets up Support Program to Help Patients Participate in Clinical Trials

For many patients battling deadly diseases, getting access to a clinical trial can be life-saving, but it can also be very challenging. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved a concept plan to make it financially and logistically easier for patients to take part in CIRM-funded clinical trials.

The plan will create a Patient Support Program (PSP) to provide support to California patients being evaluated or enrolled in CIRM-supported clinical trials, with a particular emphasis on helping underserved populations.

“Helping scientists develop stem cell and gene therapies is just part of what we do at CIRM. If those clinical trials and resulting therapies are not accessible to the people of California, who are making all this possible, then we have not fulfilled our mission.” says Maria T. Millan, M.D., President and CEO of CIRM.

The Patient Support Plan will offer a range of services including:

  • Clinical trial navigation, directing patients to appropriate CIRM-supported clinical trials.
  • Logistical support for patients being evaluated or enrolled in clinical trials.
  • Financial support for under resourced and underserved populations in CIRM-supported clinical trials, including the CIRM Patient Assistance Fund (PAF).  This support includes transportation/travel expenses, such as gasoline, tolls, parking, airfare, taxi, train, lodging, and meals during travel.
  • Providing nurse navigator support for the psychosocial, emotional, and practical needs of patients and their families.

The funds for the PSP are set aside under Proposition 14, the voter-approved initiative that re-funded CIRM in 2020. Under Prop 14 CIRM money that CIRM grantees earn from licensing, inventions or technologies is to be spent “offsetting the costs of providing treatments and cures arising from institute-funded research to California patients who have insufficient means to purchase such treatment or cure, including the reimbursement of patient-qualified costs for research participants.”

Currently, the CIRM Licensing Revenues and Royalties Fund has a balance of $15.6 million derived from royalty payments.

“The patient support program and financial resources will not only help patients in need, it will also help increase the likelihood that these clinical trials will succeed,” says Sean Turbeville, Ph.D., Vice President of Medical Affairs and Policy at CIRM. “We know cell and gene therapies can be particularly challenging for patients and their families. The financial challenges, the long-distance traveling, extended evaluation, and family commitments can make it difficult to enroll and retain patients. The aim of the PSP is to change that.”

The overall objective of this funding opportunity is to establish a statewide program that, over five years, is expected to support hundreds of patients in need as they participate in the growing number of CIRM-supported clinical trials. The program is expected to cost between $300,000 to $500,000 a year. That money will come from the Medical Affairs budget and not out of the patient assistance fund.

The first phase of the program will identify an organization, through a competitive process, that has the expertise to provide patient support services including:

  • Maintaining a call and support center.
  • Assessing patient eligibility for financial assistance.
  • Reporting to CIRM on patients needs and center performance

 You can find more information about the Patient Support Program on our website here and here.

So far, some encouraging news for stem cell clinical trial treating epilepsy

Neurona Therapeutics is testing a new therapy for a drug-resistant form of epilepsy and has just released some encouraging early findings. The first patient treated went from having more than 30 seizures a month to just four seizures over a three-month period.

This clinical trial, funded by the California Institute for Regenerative Medicine (CIRM), is targeting  mesial temporal lobe epilepsy (MTLE), one of the most common forms of epilepsy. Because the seizures caused by MTLE are frequent, they can be particularly debilitating and increase the risk of a decreased quality of life, depression, anxiety and memory impairment.

Neurona’s therapy, called NRTX-1001, consists of a specialized type of neuronal cell derived from embryonic stem cells.  Neuronal cells are messenger cells that transmit information between different areas of the brain, and between the brain and the rest of the nervous system.

NRTX-1001 is injected into the brain in the area affected by the seizures where it releases neurotransmitters or chemical messengers that will block the signals in the brain causing the epileptic seizures.

The first patient treated had a nine-year history of epilepsy and, despite being on anti-epileptic medications, was experiencing dozens of seizures a month. Since the therapy he has had only four seizures in three months. The therapy hasn’t produced any serious side effects.

In a news release Dr. Cory Nicholas, Neurona’s President and CEO, said while this is only one patient, it’s good news.

“The reduced number of seizures reported by the first person to receive NRTX-1001 is very encouraging, and we remain cautiously optimistic that this reduction in seizure frequency will continue and extend to others entering this cell therapy trial. NRTX-1001 administration has been well tolerated thus far in the clinic, which is in line with the extensive preclinical safety data collected by the Neurona team. With recent clearance from the Data Safety Monitoring Board we are excited to continue patient enrollment. We are very grateful to these first participants, and thank the clinical teams for the careful execution of this pioneering study.”

CIRM has been a big supporter of this work from the early Discovery stage work to this clinical trial. That’s because when we find something promising, we want to do everything we can to help it live up to its promise.

Funding a Clinical Trial for a Functional Cure for HIV

The use of antiretroviral drugs has turned HIV/AIDS from a fatal disease to one that can, in many cases in the US, be controlled. But these drugs are not a cure. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) voted to approve investing $6.85 million in a therapy that aims to cure the disease.

This is the 82nd clinical trial funded by CIRM.

There are approximately 38 million people worldwide living with HIV/AIDS. And each year there are an estimated 1.5 million new cases. The vast majority of those living with HIV do not have access to the life-saving antiretroviral medications that can keep the virus under control. People who do have access to the medications face long-term complications from them including heart disease, bone, liver and kidney problems, and changes in metabolism.

The antiretroviral medications are effective at reducing the viral load in people with HIV, but they don’t eliminate it. That’s because the virus that causes AIDS can integrate its DNA into long-living cells in the body and remain dormant. When people stop taking their medications the virus is able to rekindle and spread throughout the body.

Dr. William Kennedy and the team at Excision Bio Therapeutics have developed a therapeutic candidate called EBT-101. This is the first clinical study using the CRISPR-based platform for genome editing and excision of the latent form of HIV-1, the most common form of the virus that causes AIDS in the US and Europe. The goal is to eliminate or sufficiently reduce the hidden reservoirs of virus in the body to the point where the individual is effectively cured.

“To date only a handful of people have been cured of HIV/AIDS, so this proposal of using gene editing to eliminate the virus could be transformative,” says Dr. Maria Millan, President and CEO of CIRM. “In California alone there are almost 140,000 people living with HIV. HIV infection continues to disproportionately impact marginalized populations, many of whom are unable to access the medications that keep the virus under control. A functional cure for HIV would have an enormous impact on these communities, and others around the world.”

In a news release announcing they had dosed the first patient, Daniel Dornbusch, CEO of Excision, called it a landmark moment. “It is the first time a CRISPR-based therapy targeting an infectious disease has been administered to a patient and is expected to enable the first ever clinical assessment of a multiplexed, in vivo gene editing approach. We were able to reach this watershed moment thanks to years of innovative work by leading scientists and physicians, to whom we are immensely grateful. With this achievement, Excision has taken a major step forward in developing a one-time treatment that could transform the HIV pandemic by freeing affected people from life-long disease management and the stigma of disease.”

The Excision Bio Therapeutics team also scored high on their plan for Diversity, Equity and Inclusion. Reviewers praised them for adding on a partnering organization to provide commitments to serve underserved populations, and to engaging a community advisory board to help guide their patient recruitment.

CIRM has already invested almost $81 million in 20 projects targeting HIV/AIDS, including four clinical trials.

Fast Track Designation for a therapy making transplants safer for children with a fatal immune disorder

Bone marrow transplant

For children born with severe combined immunodeficiency (SCID) life can be very challenging. SCID means they have no functioning immune system, so even a simple infection can prove life threatening. Left untreated, children with SCID often die in the first few years of life.

There are stem cell/gene therapies funded by the California Institute for Regenerative Medicine (CIRM), such as ones at UCLA and UCSF/St. Judes, but an alternative method of treating, and even curing the condition, is a bone marrow or hematopoietic stem cell transplant (HCT). This replaces the child’s blood supply with one that is free of the SCID mutation, which helps restore their immune system.

However, current HCT methods involve the use of chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. This approach is toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.

To change that, Dr. Judy Shizuru at Stanford University, with CIRM funding, developed an antibody that can direct the patient’s own immune cells to kill diseased blood stem cells, creating the room needed to transplant new, healthy cells. The goal was to make stem cell transplants safer and more effective for the treatment of many life-threatening blood disorders.

That approach, JSP191, is now being championed by Jasper Therapeutics and they just got some very good news from the Food and Drug Administration (FDA). The FDA has granted JSP191 Fast Track Designation, which can speed up the review of therapies designed to treat serious conditions and fill unmet medical needs.

In a news release, Ronald Martell, President and CEO of Jasper Therapeutics, said this is good news for the company and patients: “This new Fast Track designation recognizes the potential role of JSP191 in improving clinical outcomes for these patients and will allow us to more closely work with the FDA in the upcoming months to determine a path toward a Biologics License Application (BLA) submission.”

Getting a BLA means Jasper will be able to market the antibody in the US and make it available to all those who need it.

This is the third boost from the FDA for Jasper. Previously the agency granted JSP191 both Orphan and Rare Pediatric Disease designations. Orphan drug designation qualifies sponsors for incentives such as tax credits for clinical trials. Rare Pediatric Disease designation means that if the FDA does eventually approve JSP191, then Jasper can apply to receive a priority review of an application to use the product for a different disease, such as someone who is getting a bone marrow transplant for sickle cell disease or severe auto immune diseases.

The race to cure sickle cell disease

September is National Sickle Cell Awareness Month, a time to refocus our efforts to find new treatments, even a cure, for people with sickle cell disease. Until we get those, CIRM remains committed to doing everything we can to reduce the stigma and bias that surrounds it.

Sickle cell disease (SCD) is a rare, inherited blood disorder in which normally smooth and round red blood cells may become sickle-shaped and harden. These blood cells can clump together and clog up arteries, causing severe and unpredictable bouts of pain, organ damage, vision loss and blindness, strokes and premature death.

There is a cure, a bone marrow transplant from someone who is both a perfect match and doesn’t carry the SCD trait. However, few patients are able to find that perfect match and even if they do the procedure carries risks.

That’s why the California Institute for Regenerative Medicine (CIRM) has invested almost $60 million in 14 projects, including five clinical trials targeting the disease. It’s also why we are partnering with the National Heart, Lung and Blood Institute (NHLBI) in their Cure Sickle Cell Initiative (CureSCi).

As part of the events around National Sickle Cell Awareness Month the NHLBI is launching the Gene Therapy to Reduce All Sickle Pain (GRASP) Trial and hosting a special Journeys in Mental Health Webinar on September 27th

The GRASP Trial is a Phase 2 trial that will take place at various locations throughout the country.  It’s a collaboration between the NHLBI and CIRM. Researchers are testing whether a gene therapy approach can improve or eliminate sickle cell pain episodes.  

Shortly after being born, babies stop producing blood containing oxygen-rich fetal hemoglobin and instead produce blood with the adult hemoglobin protein. For children with sickle cell disease, the transition from the fetal to the adult form of hemoglobin marks the onset of anemia and the painful symptoms of the disorder.

Scientists previously discovered that the BCL11A gene helps to control fetal hemoglobin and that decreasing the expression of this gene can increase the amount of fetal hemoglobin while at the same time reducing the amount of sickle hemoglobin in blood.  This could result in boosting the production of normal shaped red blood cells with a goal of curing or reducing the severity of sickle cell disease.   

The approach used in this trial is similar to a bone marrow transplant, but instead of using donor stem cells, this uses the patient’s own blood stem cells with new genetic information that instructs red blood cells to silence the expression of the BCL11A gene. This approach is still being studied to make sure that it is safe and effective, but it potentially has the advantage of eliminating some of the risks of other therapies. 

In this trial, patients will have to spend some time in an inpatient unit as they undergo chemotherapy to kill some bone marrow blood stem cells and create room for the new, gene-modified cells to take root.

The trial is based on a successful pilot/phase 1 study which showed it to be both safe and effective in the initial 10 patients enrolled in the trial.

For more information about the trial, including inclusion/exclusion criteria and trial locations, please visit the CureSCi GRASP trial page.

Nancy Rene, a sickle cell disease patient advocate, says while clinical trials like this are obviously important, there’s another aspect of the treatment of people with the disease that is still too often overlooked.

“As much as I applaud CIRM for the work they are doing to find a therapy or cure for Sickle Cell, I am often dismayed by the huge gulf between research protocols and general medical practice. For every story I hear about promising research, there is often another sad tale about a sickle cell patient receiving inadequate care. This shouldn’t be an either/or proposition. Let’s continue to support ground-breaking research while we expand education and training for medical professionals in evidenced based treatment. I look forward to the day when sickle cell patients receive the kind of treatment they need to lead healthy, pain-free lives.”

CIRM-funded stem cell-gene therapy shows promise in ALS safety trial

Senior author of the study Clive Svendsen, PhD (center)

With funding support from the California Institute for Regenerative Medicine (CIRM), Cedars-Sinai investigators have developed an investigational therapy using support cells and a protective protein that can be delivered past the blood-brain barrier. This combined stem cell and gene therapy can potentially protect diseased motor neurons in the spinal cord of patients with amyotrophic lateral sclerosis, a fatal neurological disorder known as ALS or Lou Gehrig’s disease. 

In the first trial of its kind, the Cedars-Sinai team showed that delivery of this combined treatment is safe in humans. The findings were reported in the peer-reviewed journal Nature Medicine

What causes ALS? 

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. About 6,000 people are diagnosed with ALS each year in the U.S., and the average survival time is two to five years.  

The disease results when the cells in the brain or spinal cord that instruct muscles to move—called motor neurons—die off. People with the disease lose the ability to move their muscles and, over time, the muscles atrophy and people become paralyzed and eventually die. There is no effective therapy for the disease. 

Using Stem Cells to Treat ALS 

In a news release, senior author Clive Svendsen, PhD, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, says using stem cells shows lots of promise in treating patients with ALS.  

“We were able to show that the engineered stem cell product can be safely transplanted in the human spinal cord. And after a one-time treatment, these cells can survive and produce an important protein for over three years that is known to protect motor neurons that die in ALS,” Svendsen says.  

Aimed at preserving leg function in patients with ALS, the engineered cells could pave the way to a therapeutic option for this disease that causes progressive muscle paralysis, robbing people of their ability to move, speak and breathe.   

The study used stem cells originally designed in Svendsen’s laboratory to produce a protein called glial cell line-derived neurotrophic factor (GDNF). This protein can promote the survival of motor neurons, which are the cells that pass signals from the brain or spinal cord to a muscle to enable movement.  

In patients with ALS, diseased glial cells can become less supportive of motor neurons, and these motor neurons progressively degenerate, causing paralysis.   

By transplanting the engineered protein-producing stem cells in the central nervous system, where the compromised motor neurons are located, these stem cells can turn into new supportive glial cells and release the protective protein GDNF, which together helps the motor neurons stay alive.   

Ensuring Safety in the Trial 

The primary goal of the trial was to ensure that delivering the cells releasing GDNF to the spinal cord did not have any safety issues or negative effects on leg function.   

In this trial, none of the 18 patients treated with the therapy—developed by Cedars-Sinai scientists and funded by CIRM—had serious side effects after the transplantation, according to the data. 

Because patients with ALS usually lose strength in both legs at a similar rate, investigators transplanted the stem cell-gene product into only one side of the spinal cord so that the therapeutic effect on the treated leg could be directly compared to the untreated leg.  

After the transplantation, patients were followed for a year so the team could measure the strength in the treated and untreated legs. The goal of the trial was to test for safety, which was confirmed, as there was no negative effect of the cell transplant on muscle strength in the treated leg compared to the untreated leg.    

What’s Next? 

Investigators expect to start a new study with more patients soon. They will be targeting lower in the spinal cord and enrolling patients at an earlier stage of the disease to increase the chances of seeing effects of the cells on the progression of ALS. 

“We are very grateful to all the participants in the study,” said Svendsen. “ALS is a very tough disease to treat, and this research gives us hope that we are getting closer to finding ways to slow down this disease.”   

The Cedars-Sinai team is also using the GDNF-secreting stem cells in another CIRM-funded clinical trial for ALS, transplanting the cells into a specific brain region, called the motor cortex that controls the initiation of movement in the hand. The clinical trial is also funded by CIRM. 

The California Institute for Regenerative Medicine (CIRM) remains committed to funding research and clinical trials to treat ALS. To date, CIRM has provided $93 million in funding for research to treat ALS.  

Read the original source release of the study here.  

How stem cells helped Veronica fight retinitis pigmentosa and regain her vision

Veronica and Elliott

Growing up Veronica McDougall thought everyone saw the world the way she did; blurry, slightly out-of-focus and with tunnel vision.  As she got older her sight got worse and even the strongest prescription glasses didn’t help. When she was 15 her brother tried teaching her to drive. One night she got into the driver’s seat to practice and told him she couldn’t see anything. Everything was just black. After that she stopped driving.   

Veronica says high school was really hard for her, but she managed to graduate and go to community college. As her vision deteriorated, she found it was increasingly hard to read the course work and impossible to see the assignments on the blackboard. Veronica says she was lucky to have some really supportive teachers — including the now First Lady Jill Biden — but eventually she had to drop out.  

Getting a diagnosis

When she was 24, she went to see a specialist who told her she had retinitis pigmentosa, a rare degenerative condition that would eventually leave her legally blind. She says it felt like a death sentence. “All of my dreams of becoming a nurse, of getting married, of having children, of traveling – it all just shattered in that moment.” 

Veronica says she went from being a happy, positive person to an angry depressed one. She woke up each morning terrified, wondering, “Is this the day I go blind?” 

Then her mother learned about a CIRM-funded clinical trial with a company called jCyte. Veronica applied to be part of it, was accepted and was given an injection of stem cells in her left eye. She says over the course of a few weeks, her vision steadily improved. 

“About a month after treatment, I was riding in the car with my mom and suddenly, I realized I could see her out of the corner of my eye while looking straight ahead. That had never, ever happened to me before. Because, I had been losing my peripheral vision at a young age without realizing that until up to that point, I had never had that experience.” 

A second chance at life

She went back to college, threw herself into her studies, started hiking and being more active. She says it was as if she was reborn. But in her senior year, just as she was getting close to finishing her degree, her vision began to deteriorate again. Fortunately, she was able to take part in a second clinical trial, and this time her vision came back stronger than ever. 

“I’m so grateful to the researchers who gave me my sight back with the treatment they have worked their entire lives to develop. I am forever grateful for the two opportunities to even receive these two injections and to be a part of an amazing experience to see again. I feel so blessed! Thank you for giving me my life back.” 

And in getting her life back, Veronica had a chance to give life. When she was at college she met and starting dating Robert, the man who was to become her partner. They now have a little boy, Elliott.  

As for the future, Veronica hopes to get a second stem cell therapy to improve her vision even further. Veronica’s two treatments were in her left eye. She is hoping that the Food and Drug Administration will one day soon approve jCyte’s therapy, so that she can get the treatment in her right eye. Then, she says, she’ll be able to see the world as the rest of us can.  

CIRM has invested more than $150 million in programs targeting vision loss, including four clinical trials for retinitis pigmentosa

The researcher who is following her bliss, and tackling diseases of aging at the same time

Dr. Jill Helms, and associate! Photo courtesy Stanford University

Jill Helms is not your average Stanford University faculty member. Yes, she is a professor in the Department of Surgery. Yes, she has published lots of scientific studies. Yes, she is a stem cell scientist (funded by CIRM). And yes, she is playing a leading role in Ankasa Regenerative Therapeutics, a company focused on tissue repair and regeneration. But she is so much more than all that.  

She is a brilliant public speaker, a fashionista, and has ridden her horse to work (well, Stanford is referred to as The Farm, so why not!) and she lives on a farm of her own called “Follow Your Bliss.” The name comes from philosopher Joseph Campbell who wrote, “If you follow your bliss, you put yourself on a kind of path that has been there all the while, waiting for you. And the life you ought to be living is the one you are living.”  

Dr. Helms says that pretty much sums up her life. She says she feels enormously blessed.  

Well, we felt enormously blessed when she agreed to sit down with us and chat about her work, her life and her love of fashion for the California Institute for Regenerative Medicine podcast, Talking ‘Bout (re)Generation.  

We hope you enjoy the latest episode! 

How CIRM contributed to City of Hope study helping man with HIV into long-term remission

The news that a stem cell transplant at City of Hope helped a man with HIV go into long-term remission made banner headlines around the world. As it should. It’s a huge achievement, particularly as the 66-year-old man had been living with HIV since 1988.

What wasn’t reported was that work supported by the California Institute for Regenerative Medicine played a role in making that happen.

The Stem Cell Transplant

First the news. In addition to living with HIV the man was diagnosed with acute leukemia. Doctors at City of Hope found a donor who was not only a perfect match to help battle the patient’s leukemia, but the donor also had a rare genetic mutation that meant they were resistant to most strains of HIV.

In transplanting blood stem cells from the donor to the patient they were able to send both his leukemia and HIV into remission. The patient stopped taking all his antiretroviral medications 17 months ago and today has no detectable levels of HIV.

In a news release  City of Hope hematologist Ahmed Aribi, M.D., said the patient didn’t experience any serious complications after the procedure.

“This patient had a high risk for relapsing from AML [acute myeloid leukemia], making his remission even more remarkable and highlighting how City of Hope provides excellent care treating complicated cases of AML and other blood cancers.”

It’s a remarkable achievement and is only the fifth time that a patient with both HIV and leukemia has been put into remission after a transplant from an HIV-resistant donor.

CIRM’s Contribution

So, what does that have to do with CIRM? Well, CIRM’s Alpha Clinics Network helped City of Hope get this case approved by an Institutional Review Board (IRB) and also helped in collecting and shipping the donor blood. In addition, part of the Alpha Clinics team at University of California San Diego helped with the reservoir analysis of blood and gut biopsies to check for any remaining signs of HIV.

It’s a reminder that this kind of achievement is a team effort and CIRM is very good at creating and supporting teams. The Alpha Clinics Network is a perfect example. We created it because there was a need for a network of world-class medical facilities with the experience and expertise to deliver a whole new kind of therapy. The Network has been remarkably successful in doing that with more than 200 clinical trials, taking care of more than 1,000 patients, and treating more than 40 different diseases.

This year our Board approved expanding the number of these clinics to better serve the people of California.

While the role of the Alpha Clinics Network in helping this one patient may seem relatively small, it was also an important one. And we are certainly not stopping here. We have invested more than $79 million in 19 different projects targeting HIV/AIDS, include four clinical trials.

We are in this for the long term and results like the man who had HIV and is now in remission are a sign we are heading in the right direction.

Stem Cell Agency funds clinical trial targeting scarred urethras

A urethral stricture is scarring of the tube that carries urine out of the body. If left untreated it can be intensely painful and lead to kidney stones and infections. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) is investing more than $3.8 million in a Phase 1 clinical trial to create a stem cell-based therapy for the condition.

This is the 81st clinical trial that CIRM has funded.

When a scar, or stricture, forms along the urethra it impedes the flow of urine and causes other complications. James Yoo, M.D., Ph.D., and his team at Wake Forest University Health Sciences will use epithelial and smooth muscle cells, taken from the patient’s bladder, and layer them on to a synthetic tubular scaffold. The tube will then be surgically implanted inside the urethra.

The goal is for the progenitor cells to support self-renewal of the tissue and for the entire structure to become integrated into the surrounding tissue and become indistinguishable from it, restoring normal urinary function. Dr. Yoo and his team believe their approach has the potential to be effective for at least a decade.

“While not immediately life-threatening, urethral strictures lead to multiple health complications that impair quality of life and predispose to kidney dysfunction,” says Dr. Maria T. Millan, President and CEO of CIRM. “Developing an effective and durable treatment would significantly impact lives and has the potential to decrease the cumulative healthcare costs of treating recurrent kidney stones, infections and downstream kidney complications, especially of long-segment urethral strictures.”