NHLBI

The race to cure sickle cell disease

/ Kevin McCormack / Leave a comment

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.”

Two reasons to remember June 19th

/ Kevin McCormack / Leave a comment

Today marks two significant events for the Black community. June 19th is celebrated as Juneteenth, the day when federal troops arrived in Galveston, Texas to ensure that the enslaved people there were free. That moment came two and a half years after President Abraham Lincoln signed the Emancipation Proclamation into law.

June 19th is also marked as World Sickle Cell Awareness Day. It’s an opportunity to raise awareness about a disease that affects around 100,000 Americans, most of them Black, and the impact it has on the whole family and entire communities.

Sickle cell disease (SCD) is an inherited blood disorder that is caused by a genetic mutation. Instead of red blood cells being smooth and round and flowing easily through arteries and veins, the cells are sickle shaped and brittle. They can clog up arteries and veins, cutting off blood to vital organs, causing intense pain, organ damage and leading to premature death.

SCD can be cured with a bone marrow transplant, but that’s a risky procedure and most people with SCD don’t have a good match. Medications can help keep it under control but cannot cure it. People with SCD live, on average, 30 years less than a healthy adult.

CIRM has invested almost $60 million in 13 different projects, including five clinical trials, to try and develop a cure for SCD. There are encouraging signs of progress. For example, in July of 2020, Evie Junior took part in a CIRM-funded clinical trial where his own blood stem cells were removed then, in the laboratory, were genetically modified to repair the genetic mutation that causes the disease. Those cells were returned to him, and the hope is they’ll create a sickle cell-free blood supply. Evie hasn’t had any crippling bouts of pain or had to go to the hospital since his treatment.

Evie Junior: Photo by Jaquell Chandler

CIRM has also entered into a unique partnership with the National Heart, Lung and Blood Institute (NHLBI) to co-fund cell and gene therapy programs under the NIH “Cure Sickle Cell” initiative.  The goal is to markedly accelerate the development of cell and gene therapies for SCD.

“There is a real need for a new approach to treating SCD and making life easier for people with SCD and their families,” says Adrienne Shapiro, the mother of a daughter with SCD and the co-founder of Axis Advocacy, a sickle cell advocacy and education organization. “Finding a cure for Sickle Cell would mean that people like my daughter would no longer have to live their life in short spurts, constantly having their hopes and dreams derailed by ER visits and hospital stays.  It would mean they get a chance to live a long life, a healthy life, a normal life.”

We will all keep working together to advance this research and develop a cure. Until then Juneteenth will be a reminder of the work that still lies ahead.

Board Funds Fifteen Bridges to Stem Cell Research and Therapy Programs Across California and New Sickle Cell Disease Trial

/ Yimy Villa / 2 Comments

Yesterday the governing Board of the California Institute for Regenerative Medicine (CIRM) awarded $8.39 million to the University of California, San Francisco (UCSF) to fund a clinical trial for sickle cell disease (SCD).  An additional $51.08 million was awarded to fifteen community colleges and universities across California to fund undergraduate and master’s level programs that will help train the next generation of stem cell researchers. 

SCD is an inherited blood disorder caused by a single gene mutation that changes a single base in the B globin gene leading to the production of defective hemoglobin that polymerizes and damages red blood cells thus the “sickle” shaped red blood cells.  The damaged cells cause blood vessels to occlude/close up and that can lead to multiple organ damage as well as reduced quality of life and life expectancy. 

Mark Walters, M.D., and his team at UCSF Benioff Children’s Hospital Oakland will be conducting a clinical trial that uses CRISPR-Cas9 gene editing technology to correct the genetic mutation in the blood stem cells of patients with severe SCD.  The corrected blood stem cells will then be reintroduced back into patients with the goal of correcting the defective hemoglobin and thus producing functional, normal shaped red blood cells.

This clinical trial will be eligible for co-funding under the landmark agreement between CIRM and the National Heart, Lung, and Blood Institute (NHLBI) of the NIH.  The CIRM-NHLBI agreement is intended to co-fund cell and gene therapy programs under the NHLBI’s “Cure Sickle Cell” initiative.  The goal is to markedly accelerate the development of cell and gene therapies for SCD. CIRM has previously funded the preclinical development of this therapy through a Translational award as well as its IND-enabling studies through a Late Stage Preclinical award in partnership with NHLBI.

The CIRM Bridges to Stem Cell Research and Therapy program provides undergraduate and master’s students with the opportunity to take stem cell related courses and receive hands on experience and training in a stem cell research related laboratory at a university or biotechnology company.  Fifteen institutions received a total of $51.08 million to carry out these programs to train the next generation of scientists.

The awards are summarized in the table below.

ApplicationTitleInstitutionAward Amount
  EDUC2-12607Bridges to Stem Cell Research and Therapy at Pasadena City College  Pasadena City College$3,605,500
  EDUC2-12611CIRM Bridges to Stem Cell Research and Therapy Training Grant  CSU San Marcos$3,606,500
  EDUC2-12617Bridges to Stem Cell Research Internship Program  San Diego State University$3,606,500
EDUC2-12620CIRM Bridges 3.0  Humboldt State$3,605,495
  EDUC2-12638CIRM Regenerative Medicine and Stem Cell Research Biotechnology Training Program  CSU Long Beach$3,276,500
    EDUC2-12677Stem Cell Internships in Laboratory-based Learning (SCILL) continue to expand the scientific workforce for stem cells research and therapies.  San Jose State University$3,606,500
  EDUC2-12691Strengthening the Pipeline of Master’s-level Scientific and Laboratory Personnel in Stem Cell Research  CSU Sacramento$2,946,500
EDUC2-12693CIRM Bridges Science Master’s Program  San Francisco State University$3,606,500
      EDUC2-12695CIRM Graduate Student Training in Stem Cell Sciences in the Stem Cell Technology and Lab Management Emphasis of the MS Biotechnology Program  CSU Channel Islands$3,606,500
  EDUC2-12718CSUN CIRM Bridges 3.0 Stem Cell Research & Therapy Training Program  CSU Northridge$3,606,500
      EDUC2-12720Stem Cell Scholars: a workforce development pipeline, educating, training and engaging students from basic research to clinical translation.  CSU San Bernardino$3,606,500
  EDUC2-12726Training Master’s Students to Advance the Regenerative Medicine Field  Cal Poly San Luis Obispo$3,276,500
  EDUC2-12730Building Career Pathways into Stem Cell Research and Therapy Development  City College of San Francisco$2,706,200
      EDUC2-12734Bridges to Stem Cell Research and Therapy: A Talent Development Program for Training Diverse Undergraduates for Careers in Regenerative Medicine  CSU Fullerton$3,606,500
  EDUC2-12738CIRM Bridges to Stem Cell Research and Therapy  Berkeley City College  $2,806,896

“We are pleased to fund a promising trial for sickle cell disease that uses the Nobel Prize winning gene editing technology CRISPR-Cas9,” says Maria T. Millan, M.D., President and CEO of CIRM.  “This clinical trial is a testament to how the CIRM model supports promising early-stage research, accelerates it through translational development, and advances it into the clinics. As the field advances, we must also meet the demand for promising young scientists.  The CIRM Bridges programs across the state of California will provide students with the tools and resources to begin their careers in regenerative medicine.”

Hitting our goals: regulatory reform

/ Kevin McCormack / Leave a comment

Way, way back in 2015 – seems like a lifetime ago doesn’t it – the team at CIRM sat down and planned out our Big 6 goals for the next five years. The end result was a Strategic Plan that was bold, ambitious and set us on course to do great things or kill ourselves trying. Well, looking back we can take some pride in saying we did a really fine job, hitting almost every goal and exceeding them in some cases. So, as we plan our next five-year Strategic Plan we thought it worthwhile to look back at where we started and what we achieved. We are going to start with Regulatory Reform.

The political landscape in 2015 was dramatically different than it is today. Compared to more conventional drugs and therapies stem cells were considered a new, and very different, approach to treating diseases and disorders. At the time the US Food and Drug Administration (FDA) was taking a very cautious approach to approving any stem cell therapies for a clinical trial.

A survey of CIRM stakeholders found that 70% said the FDA was “the biggest impediment for the development of stem cell treatments.” One therapy, touted by the FDA as a success story, had such a high clinical development hurdle placed on it that by the time it was finally approved, five years later, its market potential had significantly eroded and the product failed commercially. As one stakeholder said: “Is perfect becoming the enemy of better?”

So, we set ourselves a goal of establishing a new regulatory paradigm, working with Congress, academia, industry, and patients, to bring about real change at the FDA and to find ways to win faster approval for promising stem cell therapies, without in any way endangering patients.

It seemed rather ambitious at the time, but achieving that goal happened much faster than any of us anticipated. With a sustained campaign by CIRM and other industry leaders, working with the patient advocacy groups, the FDA, Congress, and President Obama, the 21st Century Cures Act was signed into law on December 13, 2016.

President Obama signs the 21st Century Cures Act.
Photo courtesy of NBC News

The law did something quite radical; it made the perspectives of patients an integral part of the FDA’s decision-making and approval process in the development of drugs, biological products and devices. And it sped up the review process by:

In a way the FDA took its foot off the brake but didn’t hit the accelerator, so the process moved faster, but in a safe, manageable way.

Fast forward to today and eight projects that CIRM funds have been granted RMAT designation. We have become allies with the FDA in helping advance the field. We have created a unique partnership with the National Heart, Lung and Blood Institute (NHLBI) to support the Cure Sickle Cell initiative and accelerate the development of cell and gene therapies for sickle cell disease.

The landscape has changed since we set a goal of regulatory reform. We still have work to do. But now we are all working together to achieve the change we all believe is both needed and possible.

A Month of CIRM: Where we’ve been, where we’re going

/ Kevin McCormack / Leave a comment

All this month we are using our blog and social media to highlight a new chapter in CIRM’s life, thanks to the voters approving Proposition 14. We are looking back at what we have done since we were created in 2004, and also looking forward to the future. We kick off this event with a letter from our the Chair of our Board, Jonathan Thomas.

When voters approved Proposition 14 last November, they gave the Stem Cell Agency a new lease on life and a chance to finish the work we began with the approval of Proposition 71 in 2004. It’s a great honor and privilege. It’s also a great responsibility. But I think looking back at what we have achieved over the last 16 years shows we are well positioned to seize the moment and take CIRM and regenerative medicine to the next level and beyond.

When we started, we were told that if we managed to get one project into a clinical trial by the time our money ran out we would have done a good job. As of this moment we have 68 clinical trials that we have funded plus another 31 projects in clinical trials where we helped fund crucial early stage research. That inexorable march to therapies and cures will resume when we take up our first round of Clinical applications under Prop 14 in March.

But while clinical stage projects are the end game, where we see if therapies really work and are safe in people, there’s so much more that we have achieved since we were created. We have invested $900 million in  basic research, creating a pipeline of the most promising stem cell research programs, as well as investing heavily on so-called “translational” projects, which move projects from basic science to where they’re ready to apply to the Food and Drug Administration (FDA) to begin clinical trials.

We have funded more than 1,000 projects, with each one giving us valuable information to help advance the science. Our funding has helped attract some of the best stem cell scientists in the world to California and, because we only fund research in California, it has persuaded many companies to either move here or open offices here to be eligible for our support. We have helped create the Alpha Stem Cell Clinics, a network of leading medical centers around the state that have the experience and expertise to deliver stem cell therapies to patients. All of those have made California a global center in the field.

That result is producing big benefits for the state. An independent Economic Impact Analysis reported that by the end of 2018 we had already helped generate an extra $10.7 billion in new sales revenue and taxes for California, hundreds of millions more in federal taxes and created more than 56,000 new jobs.

As if that wasn’t enough, we have also:

  • Helped develop the largest iPSC research bank in the world.
  • Created the CIRM Center of Excellence in Stem Cell Genomics to accelerate fundamental understanding of human biology and disease mechanisms.
  • Helped fund the construction of 12 world class stem cell institutes throughout the state.
  • Reached a unique partnership with the National Heart, Lung and Blood Institutes to find a cure for sickle cell disease.
  • Used our support for stem cell research to leverage an additional $12 billion in private funding for the field.
  • Enrolled more than 2700 patients in CIRM funded clinical trials

In many ways our work is just beginning. We have laid the groundwork, helped enable an extraordinary community of researchers and dramatically accelerated the field. Now we want to get those therapies (and many more) over the finish line and get them approved by the FDA so they can become available to many more people around the state, the country and the world.

We also know that we have to make these therapies available to all people, regardless of their background and ability to pay. We have to ensure that underserved communities, who were often left out of research in the past, are an integral part of this work and are included in every aspect of that research, particularly clinical trials. That’s why we now require anyone applying to us for funding to commit to engaging with underserved communities and to have a written plan to show how they are going to do that.

Over the coming month, you will hear more about some of the remarkable things we have managed to achieve so far and get a better sense of what we hope to do in the future. We know there will be challenges ahead and that not everything we do or support will work. But we also know that with the team we have built at CIRM, the brilliant research community in California and the passion and drive of the patient advocate community we will live up to the responsibility the people of California placed in us when they approved Proposition 14.

CIRM-Funded Clinical Trial for Sickle Cell Gives Hope to People Battling the Disease

/ Kevin McCormack / Leave a comment
Marissa Cors (right) with her mother Adrienne Shapiro

Marissa Cors has lived with Sickle Cell Disease (SCD) for more than 40 years. The co-founder of The Sickle Cell Experience Live, an online platform designed to bring more awareness to Sickle Cell Disease around the world, says it’s hard, knowing that at any moment you may have to put your life on hold to cope with another attack of excruciating pain.

“It is incredibly frustrating to have a disease that is constantly disrupting and interfering with your life. The daily pain and fatigue make it difficult to have a normal life. You may be experiencing manageable pain one minute and then a crisis will hit – knocking you to the ground with horrible pain and requiring pain management and hospitalization. It makes going to school or having a job or even a normal adult relationship near impossible.”

SCD is an inherited disease caused by a single gene mutation resulting in abnormal hemoglobin, which causes red blood cells to ‘sickle’ in shape.  Sickling of red blood cells clogs blood vessels and leads to progressive organ damage, pain crises, reduced quality of life, and early death. 

The disease affects around 100,000 Americans, mostly Black Americans but also members of the Latinx community. Marissa says coping with it is more than just a medical struggle. “Born into the cycle of fatigue, pain and fear. Depending on a healthcare system filled with institutionalized bias and racism. It is a life that is difficult on all facets.” 

CIRM is committed to trying find new treatments, and even a cure for SCD. That’s why the CIRM Board recently awarded $8,333,581 to Dr. David Williams at Boston Children’s Hospital to conduct a gene therapy clinical trial for sickle cell disease.  This is the second project that is part of an agreement between CIRM and the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, to co-fund cell and gene therapy programs under the NHLBI’s  “Cure Sickle Cell” Initiative.  The goal of this agreement is to markedly accelerate clinical development of cell and gene therapies to cure SCD.

In recent years we have made impressive strides in developing new approaches to treating sickle cell disease,” says Dr. Maria T. Millan, President & CEO of CIRM. “But we still have work to do. That’s why this partnership, this research is so important. It reflects our commitment to pushing ahead as fast as we can to find a treatment, a cure, that will help all the people battling the disease here in the U.S. and the estimated 20 million worldwide.”

The team will take a patient’s own blood stem cells and insert a novel engineered gene to silence abnormal hemoglobin and induce normal fetal hemoglobin expression.  The modified blood stem cells will then be reintroduced back into the patient.  The goal of this therapy is to aid in the production of normal shaped red blood cells, thereby reducing the severity of the disease. 

For Marissa, anything that helps make life easier will be welcome not just for people with SCD but their families and the whole community. “A stem cell cure will end generations of guilt, suffering, pain and early death. It will give SCD families relief from the financial, emotional and spiritual burden of caring someone living with SCD. It will give all of us an opportunity to have a normal life. Go to school, go to work, live with confidence.” 

NIH collaboration aims to develop affordable gene therapies for sickle cell disease and HIV

/ Yimy Villa / Leave a comment

Sickle cell disease (SCD) and HIV have a major burden on the health of impoverished communities all over the world.

Of the 38 million people living with HIV all over the world, approximately 95% reside within developing countries, with 67% in sub-Saharan Africa, half of whom are living without any treatment.

Fifteen million babies will be born with SCD globally over the next 30 years. Of those births, 75% will occur in sub-Saharan Africa. In this region, SCD is the underlying cause of 1 in 12 newborn deaths and an estimated 50-90% of infants born with SCD in developing countries will die before their 5th birthday.

It is because of this epidemic around the world that the National Institutes of Health (NIH) and The Bill & Melinda Gates Foundation have formed a collaboration, with the bold goal of advancing safe, effective and durable gene-based therapies to clinical trials in the United States and relevant countries in sub-Saharan Africa within the next seven to 10 years. The ultimate goal is to scale and implement these treatments globally in areas hardest hit by these diseases.

Through this collaboration, the NIH plans to invest at least $100 million over the next four years towards gene therapies related to SCD and HIV and in return The Bill and Melinda Gates Foundation will match this investment with an additional $100 million towards the same goal.

Currently, due to their intrinsic complexity and cost of treatment requirements, gene based therapies are generally limited to hospitals in wealthy countries. The collaborative effort between the NIH and the Gates Foundation seeks to change that by investing in the development of curative therapies that can be delivered safely, effectively and affordably in low-resource settings.

In a news release, NIH Director Dr. Francis Collins discusses the potential this agreement holds:

“This unprecedented collaboration focuses from the get-go on access, scalability and affordability of advanced gene-based strategies for sickle cell disease and HIV to make sure everybody, everywhere has the opportunity to be cured, not just those in high-income countries.”

In the same news release, Dr. Trevor Mundel, President of the Global Health Program at The Bill & Melinda Gates Foundation echoes the same sentiment:

“In recent years, gene-based treatments have been groundbreaking for rare genetic disorders and infectious diseases. While these treatments are exciting, people in low- and middle-income countries do not have access to these breakthroughs. By working with the NIH and scientists across Africa, we aim to ensure these approaches will improve the lives of those most in need and bring the incredible promise of gene therapy to the world of public health.”

Similarly, CIRM and the National Heart, Lung, and Blood Institute (NHLBI), an institute within the NIH, have entered a landmark agreement on curing SCD. CIRM has already funded one program under this agreement and has another $27 million available to fund other potential therapies.

Breaking bad news to stem cell researchers

/ Kevin McCormack / 6 Comments

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.

CIRM & NHLBI Create Landmark Agreement on Curing Sickle Cell Disease

/ Yimy Villa / Leave a comment

CIRM Board approves first program eligible for co-funding under the agreement

Adrienne Shapiro, co-founder of Axis Advocacy, with her daughter Marissa Cors, who has Sickle Cell Disease.

Sickle Cell disease (SCD) is a painful, life-threatening blood disorder that affects around 100,000 people, mostly African Americans, in the US. Even with optimal medical care, SCD shortens expected lifespan by decades.  It is caused by a single genetic mutation that results in the production of “sickle” shaped red blood cells.  Under a variety of environmental conditions, stress or viral illness, these abnormal red blood cells cause severe anemia and blockage of blood vessels leading to painful crisis episodes, recurrent hospitalization, multi-organ damage and mini-strokes.    

On April 29th the governing Board of the California Institute for Regenerative Medicine (CIRM) approved $4.49 million to Dr. Mark Walters at UCSF Benioff Children’s Hospital in Oakland to pursue a gene therapy cure for this devastating disease. The gene therapy approach uses CRISPR-Cas9 technology to correct the genetic mutation that leads to sickle cell disease. This program will be eligible for co-funding under the landmark agreement between CIRM and the National Heart, Lung and Blood Institute (NHLBI) of the NIH.

This CIRM-NHLBI agreement was finalized this month to co-fund cell and gene therapy programs under the NIH “Cure Sickle Cell” initiative.  The goal is to markedly accelerate the development of cell and gene therapies for SCD. It will deploy CIRM’s resources and expertise that has led to a portfolio of over 50 clinical trials in stem cell and regenerative medicine.     

“CIRM currently has 23 clinical stage programs in cell and gene therapy.  Given the advancements in these approaches for a variety of unmet medical needs, we are excited about the prospect of leveraging this to NIH-NHLBI’s Cure Sickle Cell Initiative,” says Maria T. Millan, M.D., the President and CEO of CIRM. “We are pleased the NHLBI sees value in CIRM’s acceleration and funding program and look forward to the partnership to accelerate cures for sickle cell disease.”

“There is a real need for a new approach to treating SCD and making life easier for people with SCD and their families,” says Adrienne Shapiro, the mother of a daughter with SCD and the co-founder of Axis Advocacy, a sickle cell advocacy and education organization. “Finding a cure for Sickle Cell would mean that people like my daughter would no longer have to live their life in short spurts, constantly having their hopes and dreams derailed by ER visits and hospital stays.  It would mean they get a chance to live a long life, a healthy life, a normal life.”

CIRM is currently funding two other clinical trials for SCD using different approaches.  One of these trials is being conducted at City of Hope and the other trial is being conducted at UCLA.

Stem Cell Agency Invests in New Immunotherapy Approach to HIV, Plus Promising Projects Targeting Blindness and Leukemia

/ Kevin McCormack / 8 Comments

HIV AIDS

While we have made great progress in developing therapies that control the AIDS virus, HIV/AIDS remains a chronic condition and HIV medicines themselves can give rise to a new set of medical issues. That’s why the Board of the California Institute for Regenerative Medicine (CIRM) has awarded $3.8 million to a team from City of Hope to develop an HIV immunotherapy.

The City of Hope team, led by Xiuli Wang, is developing a chimeric antigen receptor T cell or CAR-T that will enable them to target and kill HIV Infection. These CAR-T cells are designed to respond to a vaccine to expand on demand to battle residual HIV as required.

Jeff Sheehy

CIRM Board member Jeff Sheehy

Jeff Sheehy, a CIRM Board member and patient advocate for HIV/AIDS, says there is a real need for a new approach.

“With 37 million people worldwide living with HIV, including one million Americans, a single treatment that cures is desperately needed.  An exciting feature of this approach is the way it is combined with the cytomegalovirus (CMV) vaccine. Making CAR T therapies safer and more efficient would not only help produce a new HIV treatment but would help with CAR T cancer therapies and could facilitate CAR T therapies for other diseases.”

This is a late stage pre-clinical program with a goal of developing the cell therapy and getting the data needed to apply to the Food and Drug Administration (FDA) for permission to start a clinical trial.

The Board also approved three projects under its Translation Research Program, this is promising research that is building on basic scientific studies to hopefully create new therapies.

  • $5.068 million to University of California at Los Angeles’ Steven Schwartz to use a patient’s own adult cells to develop a treatment for diseases of the retina that can lead to blindness
  • $4.17 million to Karin Gaensler at the University of California at San Francisco to use a leukemia patient’s own cells to develop a vaccine that will stimulate their immune system to attack and destroy leukemia stem cells
  • Almost $4.24 million to Stanford’s Ted Leng to develop an off-the-shelf treatment for age-related macular degeneration (AMD), the leading cause of vision loss in the elderly.

The Board also approved funding for seven projects in the Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Application Title Institution CIRM Committed Funding
DISC2-10979 Universal Pluripotent Liver Failure Therapy (UPLiFT)

 

 Children’s Hospital of Los Angeles $1,297,512

 
DISC2-11105 Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer

 

 Stanford $1,415,016
DISC2-10973 Small Molecule Proteostasis Regulators to Treat Photoreceptor Diseases

 

 U.C. San Diego $1,160,648
DISC2-11070 Drug Development for Autism Spectrum Disorder Using Human Patient iPSCs

 

 Scripps $1,827,576
DISC2-11183 A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs

 

 University of Southern California $833,971
DISC2-11199 Modulation of the Wnt pathway to restore inner ear function

 

 Stanford $1,394,870
DISC2-11109 Regenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion Syndrome

 

 Stanford $1,415,016

Finally, the Board approved the Agency’s 2019 research budget. Given CIRM’s new partnership with the National Heart, Lung, Blood Institute (NHLBI) to accelerate promising therapies that could help people with Sickle Cell Disease (SCD) the Agency is proposing to set aside $30 million in funding for this program.

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Congresswoman Barbara Lee (D-CA 13th District)

Congresswoman Barbara Lee (D-CA 13th DIstrict)

“I am deeply grateful for organizations like CIRM and NHLBI that do vital work every day to help people struggling with Sickle Cell Disease,” said Congresswoman Barbara Lee (D-CA 13th District). “As a member of the House Appropriations Subcommittee on Labor, Health and Human Services, and Education, I know well the importance of this work. This innovative partnership between CIRM and NHLBI is an encouraging sign of progress, and I applaud both organizations for their tireless work to cure Sickle Cell Disease.”

Under the agreement CIRM and the NHLBI will coordinate efforts to identify and co-fund promising therapies targeting SCD.  Programs that are ready to start an IND-enabling or clinical trial project for sickle cell can apply to CIRM for funding from both agencies. CIRM will share application information with the NHLBI and CIRM’s Grants Working Group (GWG) – an independent panel of experts which reviews the scientific merits of applications – will review the applications and make recommendations. The NHLBI will then quickly decide if it wants to partner with CIRM on co-funding the project and if the CIRM governing Board approves the project for funding, the two organizations will agree on a cost-sharing partnership for the clinical trial. CIRM will then set the milestones and manage the single CIRM award and all monitoring of the project.

“This is an extraordinary opportunity to create a first-of-its-kind partnership with the NHLBI to accelerate the development of curative cell and gene treatments for patients suffering with Sickle Cell Disease” says Maria T. Millan, MD, President & CEO of CIRM. “This allows us to multiply the impact each dollar has to find relief for children and adults who battle with this life-threatening, disabling condition that results in a dramatically shortened lifespan.  We are pleased to be able to leverage CIRM’s acceleration model, expertise and infrastructure to partner with the NHLBI to find a cure for this condition that afflicts 100,000 Americans and millions around the globe.”

The budget for 2019 is:

Program type 2019
CLIN1 & 2

CLIN1& 2 Sickle Cell Disease

 $93 million

$30 million
TRANSLATIONAL $20 million
DISCOVER $0
EDUCATION $600K