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

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.

New Report Says CIRM Produces Big Economic Boost for California

An independent Economic Impact Report says the California Institute for Regenerative Medicine (CIRM) has had a major impact on California’s economy, creating tens of thousands of new jobs, generating hundreds of millions of dollars in new taxes, and producing billions of dollars in additional revenue for the state.

The report, done by Dan Wei and Adam Rose at the Price School of Public Policy at the University of Southern California, looked at the impacts of CIRM funding on both the state and national economy from the start of the Stem Cell Agency in 2004 to the end of 2018.

The total impacts on the California economy are estimated to be:

  • $10.7 billion of additional gross output (sales revenue)
  • $641.3 million of additional state/local tax revenues
  • $726.6 million of additional federal tax revenues
  • 56,549 additional full-time equivalent (FTE) jobs, half of which offer salaries considerably higher than the state average

Maria Millan, M.D., CIRM’s President and CEO, says the report reflects the Agency’s role in building an ecosystem to accelerate the translation of important stem cell science to solutions for patients with unmet medical needs. “CIRM’s mission on behalf of patients has been the priority from day one, but this report shows that CIRM funding brings additional benefits to the state. This report reflects how CIRM is promoting economic growth in California by attracting scientific talent and additional capital, and by creating an environment that supports the development of businesses and commercial enterprises in the state”

In addition to the benefits to California, the impacts outside of California on the US economy are estimated to be:

  • $4.7 billion of additional gross output (sales revenue)
  • $198.7 million of additional state (non-Californian) & local tax revenue
  • $208.6 million of additional federal tax revenues
  • 25,816 additional full-time equivalent (FTE) jobs

The researchers summarize their findings, saying: “In terms of economic impacts, the state’s investment in CIRM has paid handsome dividends in terms of output, employment, and tax revenues for California.”

The estimates in the report are based on the economic stimulus created by CIRM funding and by the co-funding that researchers and companies were required to provide for clinical and late-stage preclinical projects. The estimates also include:

  • Investments in CIRM-supported projects from private funders such as equity investments, public offerings and mergers and acquisitions,
  • Follow-on funding from the National Institutes of Health and other organizations due to data generated in CIRM-funded projects
  • Funding generated by clinical trials held at CIRM’s Alpha Stem Cell Clinics network

The researchers state “Nearly half of these impacts emanate from the $2.67 billion CIRM grants themselves.”

“The economic impact of California’s investment in stem and regenerative cell research is reflective of significant progress in this field that was just being born at the time of CIRM’s creation,” says Dr. Millan. “We fund the most promising projects based on rigorous science from basic research into clinical trials. We partnered with researchers and companies to increase the likelihood of success and created specialized infrastructure such as the Alpha Clinics Network to support the highest quality of clinical care and research standards for these novel approaches.  The ecosystem created by CIRM has attracted scientists, companies and capital from outside the state to California. By supporting promising science projects early on, long before most investors were ready to come aboard, we enabled our scientists to make progress that positioned them to attract significant commercial investments into their programs and into California.”

These partnerships have helped move promising therapies out of the lab and into clinical trials for companies like Orchard Therapeutics’ successful treatment for Severe Combined Immunodeficiency and Forty Seven Inc.’s innovative approach to treating cancer.

Dr. Don Kohn: Photo courtesy UCLA Jonsson Comprehensive Cancer Center

“I think one of the greatest strengths of CIRM has been their focus on development of new stem cell therapies that can become real medicines,” says UCLA and Orchard Therapeutics’ Don Kohn, M.D. “This has meant guiding academic investigators to do the things that may be second nature in industry/pharmaceutical companies but are not standard for basic or clinical research.  The support from CIRM to perform the studies and regulatory activities needed to navigate therapies through the FDA and to form alliances with biotech and pharma companies has allowed the stem cell gene therapy we developed to treat SCID babies to be advanced and licensed to Orchard Therapeutics who can make it available to patients across the country.”

Dr. Mark Chao: Photo courtesy Forty Seven Inc.

“CIRM’s support has been instrumental to our early successes and our ability to rapidly progress Forty Seven’s CD47 antibody targeting approach with magrolimab,” says Mark Chao, M.D., Ph.D., Founder and Vice President of Clinical Development at Forty Seven Inc. “ CIRM was an early collaborator in our clinical programs, and will continue to be a valued partner as we move forward with our MDS/AML clinical trials.”

The researchers say the money generated by partnerships and investments, what is called “deal-flow funding”, is still growing and that the economic benefits created by them are likely to continue for some time: “Deal-flow funding usually involves several waves or rounds of capital infusion over many years, and thus is it expected that CIRM’s past and current funding will attract increasing amounts of industry investment and lead to additional spending injections into the California economy in the years to come.”

They conclude their report by saying: “CIRM has led to California stem cell research and development activities becoming a leader among the states.”

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.

Getting the inside scoop on the stem cell agency

There’s a wonderful moment at the end of the movie The Candidate (starring Robert Redford, 87% approval on Rotten Tomatoes!) about a modern political campaign for a US Senate seat. Redford (spoiler alert) plays a come-from-behind candidate and at the end when he wins he turns to his campaign manager and says “Now what?”.

I think that’s how a lot of people associated with Proposition 71 felt when it was approved by California voters in 2004, creating CIRM. Now what? During the campaign you are so focused on crossing the finish line that when the campaign is over you have to pause because you just realized it wasn’t the finishing line, it was actually the starting line.

For us “now what” involved hiring a staff, creating oversight groups of scientists and ethics experts, developing strategies and then mechanisms for funding, and then mechanisms for tracking that funding to make sure it was being used properly. It was creating something from scratch and trying to do something that no state agency had done before.

Fifteen years later we are coming to the end of the funding provided by Prop 71 and that question keeps popping up again, “Now what?” And that’s what we are going to be talking about in our next Facebook Live.

We have three great experts on our panel. They are scientists and researchers and leaders in biotech, but also members of our CIRM Board. We rely on their experience and expertise in making key decisions and you can rely on them to pull back the curtain and talk about the things that matter most to them in helping advance our mission, and in helping secure our legacy.

Anne-Marie Duliege MD, has more than 25 years of experience in the medical world, starting out as a pediatrician and then moving into research. She has experience developing new therapies for auto-immune disorders, lung problems and infectious diseases.

Like Anne-Marie, Joe Panetta, has years of experience working in the research field, and is currently President & CEO of Biocom, the California association that advocates for more than 1,200 companies, universities and research institutes working in biotechnology.

Finally, Dave Martin MD, came to CIRM after stints at the National Institutes of Health (NIH), UC San Francisco, Genentech, Chiron and several other highly-regarded organizations. He is also the co-founder, chairman and CEO of AvidBiotics, a privately held biotechnology company in South San Francisco.

Each brings a different perspective to the work that we do at CIRM, and each enriches it not just with their intelligence and experience, but also with their compassion for the patients and commitment to our mission.

So, join us on Thursday, July 25th from noon till 1pm (PDT) for a special Facebook Live “Ask the Stem Cell Team” to understand how we got where we are, how the rest of the field is doing, and what happens next. It promises to be a fascinating hour.

Clinical trials: separating the wheat from the chaff

What do you do when the supposed solution to a problem actually turns out to be a part of the problem? That’s the situation facing people who want to direct patients to scientifically sound clinical trials. Turns out the site many were going to may be directing patients to therapies that are not only not scientifically sound, they may not even be safe.

The site in question is the www.clinicaltrials.gov website. That’s a list of all the clinical trials registered with the National Institutes of Health. In theory that should be a rock-solid list of trials that have been given the go-ahead by the Food and Drug Administration (FDA) to be tested in people. Unfortunately, the reality is very different. Many of the trials listed there have gone through the rigorous testing and approval process to earn the right to be tested in people. But some haven’t. And figuring out which is which is not easy.

The issue was highlighted by a terrific article on STAT News this week. The article’s title succinctly sums up the piece: “Stem cell clinics co-opt clinical-trials registry to market unproven therapies, critics say.”

The story highlights how clinics that are offering unproven and unapproved stem cell therapies can register their “clinical trial” on the site, even if they haven’t received FDA approval to carry out a clinical trial.

Leigh Turner, a bioethicist at the University of Minnesota and a long-time foe of these clinics, said:

“You can concoct this bogus appearance of science, call it a clinical study, recruit people to pay to participate in your study, and not only that: You can actually register on clinicaltrials.gov and have the federal government help you promote what you’re doing. That struck me as both dangerous and brilliant.”

At CIRM this is a problem we face almost every day. People call or email us asking for help finding a stem cell therapy for everything from cancer and autism to diabetes. If we are funding something or if there is one underway at one of our Alpha Stem Cell Clinics we can direct them to that particular trial. If not, the easiest thing would be to direct them to the clinicaltrials.gov site. But when you are not sure that all the programs listed are legitimate clinical trials, that’s not something we always feel comfortable doing.

As the STAT piece points out, some of the “trials” listed on the site are even being run by companies that the FDA is trying to shut down because of serious concerns about the “therapies” they are offering. One was for a Florida clinic that had blinded four people. Despite that, the clinic’s projects remain on the site where other patients can find them.

Being listed on clinicaltrials.gov gives clinics offering unproven therapies an air or legitimacy. So how can you spot a good trial from a bad one? It’s not always easy.

One red flag is if the trial is asking you to pay for the treatment. That’s considered unethical because it’s asking you to pay to be part of an experiment. Only a very few legitimate clinical trials ask patients to pay, and even then, only with permission from the FDA.

Another warning sign is anything that has a laundry list of things it can treat, everything from arthritis to Alzheimer’s. Well-designed clinical trials tend to be targeted at one condition not multiple ones.

We have put together some useful tools for patients considering taking part in a clinical trial. Here is a link to a video and infographic that tell people the questions they need to ask, and things they need to consider, before signing up for any clinical trial.

So why does the NIH continue to allow these clinics to “advertise” their programs on its website? One reason is that the NIH simply doesn’t have the bandwidth to check every listing to make sure they are legit. They have tried to make things better by including a warning, stating:

“Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Before participating in a study, talk to your health care provider and learn about the risks and potential benefits.”

The bottom line is that if you are in the market for a stem cell therapy you should approach it the way you would any potentially life-changing decision: caveat emptor, buyer beware.

The Past, the Present, and the Uncertain Future of Stem Cell Research

Ronnie, a boy who was born without a functioning immune system but who is thriving today because of CIRM funded research

When CIRM was created in 2004 the field of stem cell research was still very much in its infancy. Fast forward 15 years and it’s moving ahead at a rapid pace, probably faster than most scientists would have predicted. How fast? Find out for yourself at a free public event at UC San Diego on May 28th from 12.30 to 1.30p.

In the last 15 years CIRM has funded 53 clinical trials in everything from heart disease and stroke, to spinal cord injury, vision loss, sickle cell disease and HIV/AIDS.

UCSD was one of the first medical centers chosen to host a CIRM Alpha Stem Cell Clinic – a specialist center with the experience and expertise to deliver stem cell therapies to patients – and to date is running more than a dozen clinical trials for breast cancer, heart failure, leukemia and chronic lower back pain.

Clearly progress is being made. But the field is also facing some challenges. Funding at the federal level for stem cell research is under threat, and CIRM is entering what could be its final phase. We have enough money left to fund new projects through this year (and these are multi-year projects so they will run into 2021 or 2022) but unless there is a new round of funding we will slowly disappear. And with us, may also disappear the hopes of some of the most promising projects underway.

If CIRM goes, then projects that we have supported and nurtured through different phases of research may struggle to make it into a clinical trial because they can’t get the necessary funding.

Clearly this is a pivotal time in the field.

We will discuss all this, the past, the present and the uncertain future of stem cell research at the meeting at UC San Diego on May 28th. The doors will open at noon for registration (snacks and light refreshments will also be available) and the program runs from 12.30p to 1.30p.

The speakers are:

  • Dr. Catriona Jamieson, Director of the UC San Diego Health CIRM Alpha Stem Cell Clinic and Sanford Stem Cell Clinical Center.
  • Dr. Maria Millan, President and CEO of CIRM
  • Dr. David Higgins, CIRM Board member and Patient Advocate for Parkinson’s Disease.

And of course, we want to hear from you, so we’ll leave plenty of time for questions.

Free parking is available.

Go here for more information about the event and how you can register

Free free to share this with anyone you think might be interested in joining us and we look forward to seeing you there.

CIRM & NHLBI Create Landmark Agreement on Curing Sickle Cell Disease

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.

California’s Stem Cell Agency Accelerates Treatments to Patients

The following article is an Op Ed that appeared in today’s print version of the San Francisco Chronicle

SanFranChronicle_Web

Biotechnology was born in California in the 1970s based on the discovery out of one of its universities and California is responsible for an industry that has impacted the lives of billions of people worldwide. In 2004, the voters of California approved Proposition 71, creating the California Institute for Regenerative Medicine and setting the state on the path to becoming a global leader in stem cell research. Today the therapies resulting from the institute’s work are not just changing lives, they are already saving lives.

Lives like Evie Vaccaro, who is alive today because of a treatment CIRM is funding. Vaccaro was born with SCID, also known as “bubble baby disease,” an immune disorder that often kills babies in their first two years. Vaccaro and dozens of other babies were given stem cell treatments thanks to the institute. All are showing improvement; some are now several years past treatment and considered cured.

An accident left Jake Javier from Danville paralyzed from the chest down on the eve of his high school graduation. Javier was treated in a CIRM-funded clinical trial. Today he has regained the use of his arms and hands, is driving a car and is a sophomore at Cal Poly San Luis Obispo. Five other patients treated at the same time as Javier have all experienced improvements meaning that instead of needing round-the-clock care, they can lead independent lives.

A study by the Tufts Center for the Study of Drug Development estimated it takes at least 10 years and $2.6 billion to develop one successful drug. In 14 years, and with just $3 billion, CIRM has funded 1,000 different projects, enrolled 900 patients, and supported 49 different clinical trials targeting diseases such as cancer, kidney failure and leukemia. Four of these programs have received an expedited designation by the U.S. Food and Drug Administration, meaning they could get faster approval to help more patients

We have created a network of world class medical clinics that have expertise in delivering treatments to patients. The CIRM Alpha Clinics offer treatments based on solid science, unlike the unlicensed clinics sprouting up around California that peddle unproven and potentially harmful therapies that cost patients thousands of dollars.

CIRM has:

  • Supported the creation of 12 stem-cell research facilities in California
  • Attracted hundreds of top-tier researchers to California
  • Trained a new generation of stem-cell scientists
  • Brought clinical trials to California — for example, one targeting ALS or Lou Gehrig’s disease
  • Deployed rigorous scientific standards and support so our programs have a “seal of approval” to attract $2.7 billion in additional investments from industry and other sources.

We recently have partnered with the National Institutes of Health to break down barriers and speed up the approval process to bring curative treatments to patients with Sickle Cell Disease.

Have we achieved all we wanted to? Of course not. The first decade of CIRM’s life was laying the groundwork, developing the knowledge and expertise and refining processes so that we can truly accelerate progress. As a leader in this burgeoning field of regenerative medicine, CIRM needs to continue its mission of accelerating stem-cell treatments to patients with unmet medical needs.

Dr. Maria T. Millan is President and CEO and Jonathan Thomas, JD, PhD, is the Board Chairman of the California Institute of Regenerative Medicine. 

 

 

Overcoming one of the biggest challenges in stem cell research

Imagine you have just designed and built a new car. Everyone loves it. It’s sleek, fast, elegant, has plenty of cup holders. People want to buy it. The only problem is you haven’t built an assembly line to make enough of them to meet demand. Frustrating eh.

Overcoming problems in manufacturing is not an issue that just affects the auto industry (which won’t make Elon Musk and Tesla feel any better) it’s something that affects many other areas too – including the field of regenerative medicine. After all, what good is it developing a treatment for a deadly disease if you can’t make enough of the therapy to help the people who need it the most, the patients.

As the number of stem cell therapies entering clinical trials increases, so too does the demand for large numbers of high quality, rigorously tested stem cells. And because each of those therapies is unique, that places a lot of pressure on existing manufacturing facilities to meet the demand.

IABS panel

Representatives from the US FDA, Health Canada, EMA, FDA China, World Health Organization discuss creating a manufacturing roadmap for stem cell therapies: Photo Geoff Lomax

So, with that in mind CIRM teamed up with the International Alliance for Biological Standardization (IABS) to hold the 4th Cell Therapy Conference: Manufacturing and Testing of Pluripotent Stem Cells to try and identify the key problems and chart out solutions.

The conference brought together everyone who had a stake in this issue, including leading experts in cell manufacturing, commercial sponsors developing stem cell treatments, academic researchers, the World Health Organization, the US Food and Drug Administration (FDA), international regulatory bodies as well as patient and patient advocates too (after all, who has a greater stake in this).

Commercial sponsors and academic researchers presented case studies of how they worked through the development of manufacturing process for their stem cell treatments.

Some key points quickly emerged:

  • Scale up and quality control of stem cell manufacturing is vital to the development of stem cell treatments.
  • California is a world leader in stem cell manufacturing.
  • There have been numerous innovations in cell manufacturing that serve to support quality, quantity, performance and cost control.
  • The collective experience of the field is leading to standardization of definitions (so we all use the same language), standardization of processes to release quality cells, manufacturing and standardization of testing (so we all meet the same safety requirements).
  • Building consensus among stakeholders is important for accelerating stem cell treatments to patients.

Regulatory experts emphasized the importance of thinking about manufacturing early on in the research and product development phase, so that you can avoid problems in later stages.

There were no easy answers to many of the questions posed, but there was agreement on the importance of developing a stem cell glossary, a common set of terms and definitions that we can all use. There was also agreement on the key topics that need to continue to be highlighted such as safety testing, compatibility, early locking-in of quality processes when feasible, and scaling up.

In the past our big concern was developing the therapies. Now we have to worry about being able to manufacture enough of the cells to meet demand. That’s progress.

A technical summary is being developed and we will announce when it is available.

 

 

Stem Cell Roundup: Protein shows promise in treating deadliest form of breast cancer: mosquito spit primes our body for disease

Triple negative breast cancerTriple negative breast cancer is more aggressive and difficult to treat than other forms of the disease and, as a result, is more likely to spread throughout the body and to recur after treatment. Now a team at the University of Southern California have identified a protein that could help change that.

The research, published in the journal Nature Communications, showed that a protein called TAK1 allows cancer cells from the tumor to migrate to the lungs and then form new tumors which can spread throughout the body. There is already an FDA-approved drug called OXO that has been shown to block TAK1, but this does not survive in the blood so it’s hard to deliver to the lungs.

The USC team found a way of using nanoparticles, essentially a tiny delivery system, to take OXO and carry it to the lungs to attack the cancer cells and stop them spreading.

triple_negative_breast_cancer_particle_graphic-768x651In a news release Min Yu, the principal investigator on the team, said that although this has only been tested in mice the results are encouraging:

“For patients with triple-negative breast cancer, systemic chemotherapies are largely ineffective and highly toxic. So, nanoparticles are a promising approach for delivering more targeted treatments, such as OXO, to stop the deadly process of metastasis.”

Mosquito spit and your immune system

Mosquito

Mosquito bite: Photo courtesy National Academy of Sciences

Anyone who has ever been bitten by a mosquito knows that it can be itchy and irritable for hours afterwards. But now scientists say the impact of that bite can last for much longer, days in fact, and even help prime your body for disease.

The scientists say that every time a mosquito bites you they inject saliva into the bite to keep the blood flowing freely. But that saliva also has an impact on your immune system, leaving it more vulnerable to diseases like malaria.

OK, so that’s fascinating, and really quite disgusting, but what does it have to do with stem cells? Well, researchers at the National Institute of Health’s (NIH) Malaria and Vector Research Laboratory in Phnom Penh, Cambodia engrafted human stem cells into mice to study the problem.

They found that mice with the human stem cells developed more severe symptoms of dengue fever if they were bitten by a mosquito than if they were just injected with dengue fever.

In an article in Popular Science Jessica Manning, an infectious disease expert at the NIH, said previously we had no idea that mosquito spit had such a big impact on us:

“The virus present in that mosquito’s saliva, it’s like a Trojan horse. Your body is distracted by the saliva [and] having an allergic reaction when really it should be having an antiviral reaction and fighting against the virus. Your body is unwittingly helping the virus establish infection because your immune system is sending in new waves of cells that this virus is able to infect.”

The good news is that if we can develop a vaccine against the saliva we may be able to protect people against malaria, dengue fever, Zika and other mosquito-borne diseases.