Google eases ban on ads for stem cell therapies

What started out as an effort by Google to crack down on predatory stem cell clinics advertising bogus therapies seems to be getting diluted. Now the concern is whether that will make it easier for these clinics to lure unsuspecting patients to pay good money for bad treatments?

A little background might help here. For years Google placed no restrictions on ads by clinics that claimed their stem cell “therapies” could cure or treat all manner of ailments. Then in September of 2019 Google changed its policy and announced it was going to restrict advertisements for stem cell clinics offering unproven, cellular and gene therapies.

This new policy was welcomed by people like Dr. Paul Knoepfler, a stem cell scientist at UC Davis and longtime critic of these clinics. In his blog, The Niche, he said it was great news:

“Google Ads for stem cell clinics have definitely driven hundreds if not thousands of customers to unproven stem cell clinics. It’s very likely that many of the patients who have ended up in the hospital due to bad outcomes from clinic injections first went to those firms because of Google ads. These ads and certain particularly risky clinics also are a real threat to the legitimate stem cell and gene therapy fields.”

Now the search-engine giant seems to be adjusting that policy. Google says that starting July 11 it will permit ads for stem cell therapies approved by the US Food and Drug Administration (FDA). That’s fine. Anything that has gone through the FDA’s rigorous approval process deserves to be allowed to advertise.

The real concern lies with another adjustment to the policy where Google says it will allow companies to post ads as long as they are “exclusively educational or informational in nature, regardless of regulatory approval status.” The problem is, Google doesn’t define what constitutes “educational or informational”. That leaves the door open for these clinics to say pretty much anything they want and claim it meets the new guidelines.

To highlight that point Gizmodo did a quick search on Google using the phrase “stem cells for neuropathy” and quickly came up with a series of ads that are offering “therapies” clearly not approved by the FDA. One ad claimed it was “FDA registered”, a meaningless phrase but one clearly designed to add an air of authenticity to whatever remedy they were peddling.

The intent behind Google’s change of policy is clearly good, to allow companies offering FDA-approved therapies to advertise. However, the outcome may not be quite so worthy, and might once again put patients at risk of being tricked into trying “therapies” that will almost certainly not do them any good, and might even put them in harm’s way.

It’s hard to be modest when people keep telling you how good you are

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I have a confession. Deep down I’m shallow. So when something I am part of is acknowledged as one of the best, I delight in it (my fellow bloggers Katie and Esteban also delight in it, I am just more shameless about letting everyone know.)

And that is just what happened with this blog, The Stem Cellar. We have been named as one of the “22 best biology and stem cell blogs of 2022”. And not just by anyone. We were honored by Dr. Paul Knoepfler, a stem cell scientist, avid blogger and all-round renaissance man (full disclosure, Paul is a recipient of CIRM funding but that has nothing to do with this award. Obviously.)

We are particularly honored to be on the list because Paul includes some heavy hitters including The Signals Blog, a site that he describes this way:

“This one from our friends in Canada is fantastic. They literally have dozens of authors, which is probably the most of any stem cell-related website, and their articles include many interesting angles. They post really often too. I might rank Signal and The Stem Cellar as tied for best stem cell blog in 2021.”

Now I’m really blushing.

Other highly regarded blogs are EuroStemCell, the Mayo Clinic Regenerative Medicine Blog and Stem Cell Battles (by Don Reed, a good friend of CIRM’s)

Another one of the 22 is David Jensen’s California Stem Cell report which is dedicated to covering the work of, you guessed it, CIRM. So, not only are we great bloggers, we are apparently great to blog about. 

As a further demonstration of my modesty I wanted to point out that Paul regularly produces ‘best of’ lists, including his recent “50 influencers on stem cells on Twitter to follow” which we were also on.

The bootcamp helping in the fight against rare diseases

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Dr. Emil Kakkis at the Rare Entrepreneur Bootcamp

Imagine you or someone you love is diagnosed with a rare disease and then told, “There is no cure, there are no treatments and because it’s so rare no one is even doing any research into developing a treatment.” Sadly for millions of people that’s an all-too-common occurrence.

There are around 7,000 rare diseases affecting some 25-30 million Americans. Some of these are ultra-rare conditions where worldwide there may be only a few hundred people, or even a few dozen, diagnosed with it. And of all these rare diseases, only 5% have an approved therapy.

For the people struggling with a rare disease, finding a sense of hope in the face of all this can be challenging. Some say it feels as if they have been abandoned by the health care system. Others fight back, working to raise both awareness about the disease and funds to help support research to develop a treatment. But doing that without experience in the world of fund raising and drug development can pose a whole new series of challenges.

That’s where Ultragenyx comes into the picture. The company has a simple commitment to patients. “We aim to develop safe and effective treatments for many serious rare diseases as fast as we can, and we are committed to helping the whole rare disease community move forward by sharing our science and expertise to advance future development, whether by us or others.”

They live up to that commitment by hosting a Rare Entrepreneur Bootcamp. Every year they bring together a dozen or so patient or family organizations that are actively raising funds for a potential treatment approach and give them a 3-day crash course in what they’ll need to know to have a chance to succeed in rare disease drug development.

A panel discussion at the Rare Entrepreneur Bootcamp

Dr. Emil Kakkis, the founder of Ultragenyx, calls these advocates “warriors” because of all the battles they are going to face. He told them, “Get used to hearing no, because you are going to hear that a lot. But keep fighting because that’s the only way you get to ‘yes’.”

The bootcamp brings in experts to coach and advise the advocates on everything from presentation skills when pitching a potential investor, to how to collaborate with academic researchers, how to design a clinical trial, what they need to understand about manufacturing or intellectual property rights.

In a blog about the event, Arjun Natesan, vice president of Translational Research at Ultragenyx, wrote, “We are in a position to share what we’ve learned from bringing multiple drugs to market – and making the process easier for these organizations aligns with our goal of treating as many rare disease patients as possible. Our aim is to empower these organizations with guidance and tools and help facilitate their development of life-changing rare disease treatments.”

For the advocates it’s not just a chance to gain an understanding of the obstacles ahead and how to overcome them, it’s also a chance to create a sense of community. Meeting others who are fighting the same fight helps them realize they are not alone, that they are part of a bigger, albeit often invisible, community, working tirelessly to save the lives of their children or loved ones.  

CIRM also has a commitment to supporting the search for treatments for rare diseases. We are funding more than two dozen clinical trials, in addition to many earlier stage research projects, targeting rare conditions.

Promoting stem cell therapies, racial justice and fish breeding

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Jan Nolta, PhD, in her lab at UC Davis; Photo courtesy UC Davis

Working at CIRM you get to meet many remarkable people and Dr. Jan Nolta certainly falls into that category. Jan is the Director of the Stem Cell Program at UC Davis School of Medicine. She also directs the Institute for Regenerative Cures and is scientific director of both the Good Manufacturing Practice clean room facility at UC Davis and the California Umbilical Cord Blood Collection Program.

As if that wasn’t enough Jan is part of the team helping guide UC Davis’ efforts to expand its commitment to diversity, equity and inclusion using a variety of methods including telemedicine, to reach out into rural and remote communities.

She is on the Board of several enterprises, is the editor of the journal Stem Cells and, in her copious spare time, has dozens of aquariums and is helping save endangered species.

So, it’s no wonder we wanted to chat to her about her work and find out what makes her tick. Oh, and what rock bands she really likes. You might be surprised!

That’s why Jan is the guest on the latest edition of our podcast ‘Talking ‘Bout (re)Generation’.

I hope you enjoy it.

Joining the movement to fight rare diseases

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It’s hard to think of something as being rare when it affects up to 30 million Americans and 300 million people worldwide. But the truth is there are more than 6,000 conditions – those affecting 200,000 people or fewer – that are considered rare.  

Today, February 28th, is Rare Disease Day. It’s a day to remind ourselves of the millions of people, and their families, struggling with these diseases. These conditions are also called or orphan diseases because, in many cases, drug companies were not interested in adopting them to develop treatments.

At the California Institute for Regenerative Medicine (CIRM), we have no such reservations. In fact last Friday our governing Board voted to invest almost $12 million to support a clinical trial for IPEX syndrome. IPEX syndrome is a condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. This leads to the development of Type 1 diabetes, severe eczema, damage to the small intestines and kidneys and failure to thrive. It’s diagnosed in infancy, most of those affected are boys, and it is often fatal.

Taylor Lookofsky (who has IPEX syndrome) and his father Brian

IPEX is one of two dozen rare diseases that CIRM is funding a clinical trial for. In fact, more than one third of all the projects we fund target a rare disease or condition. Those include:

Some might question the wisdom of investing hundreds of millions of dollars in conditions that affect a relatively small number of patients. But if you see the faces of these patients and get to know their families, as we do, you know that often agencies like CIRM are their only hope.

Dr. Maria Millan, CIRM’s President and CEO, says the benefits of one successful approach can often extend far beyond one rare disease.

“Children with IPEX syndrome clearly represent a group of patients with an unmet medical need, and this therapy could make a huge difference in their lives. Success of this treatment in this rare disease presents far-reaching potential to develop treatments for a larger number of patients with a broad array of immune disorders.”

CIRM is proud to fund and spread awareness of rare diseases and invites you to watch this video about how they affect families around the world.

Making stem cell and gene therapies available and affordable for all California patients

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Developing a new therapy: Photo courtesy UCLA

There is no benefit in helping create a miraculous new therapy that can cure people and save lives if no one except the super-rich can afford it. That’s why the California Institute for Regenerative Medicine (CIRM) has made creating a roadmap to help make new treatments both available and affordable for all Californians a central pillar of its new 5-year Strategic Plan.

New treatments based on novel new technologies often seem to come with a gob-smacking price tag. When Kymriah, a CAR-T cell cancer therapy, was approved it cost $475,000 for one treatment course. When the FDA approved Zolgensma to treat spinal muscular atrophy, a genetic disorder that causes muscle wasting and weakness, the cost was $2.1 million for one dose.

Part of the pricing is due to high manufacturing cost and the specialized resources needed to deliver the treatments. The treatments themselves are showing that they can be one-and-done options for patients, meaning just one treatment may be all they need to be cured. But even with all that innovation and promise the high price may impact access to patients in need.

At CIRM we believe that if California taxpayer money has helped researchers develop a new therapy, Californians should be able to get that therapy. To try and ensure they can we have created the Accessibility and Affordability Working Group (AAWG). The groups mission is to find a way to overcome the hurdles that stand between a patient and the treatment they need.

The AAWG will work with politicians and policy makers, researchers and regulators, insurance companies and patient advocate organizations to gather the data and information needed to make these therapies available and affordable. Dr. Le Ondra Clark Harvey, a CIRM Board member and mental health advocate, says the barriers we have to confront are not just financial, they are racial and ethnic too. 

We have already created a unique model for delivering stem cell therapies to patients through our Alpha Stem Cell Clinic Network. We are now setting out to build on that with our commitment to creating Community Care Centers of Excellence. But having world-class clinics capable of delivering life-saving therapies is not enough. We also need to make sure that Californians who need these treatments can get them regardless of who they are or their ability to pay.

To learn more read out new Strategic Plan.

Overcoming obstacles and advancing treatments to patients

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UC Davis GMP Manufacturing facility: Photo courtesy UC Davis

When you are trying to do something that has never been done before, there are bound to be challenges to meet and obstacles to overcome. At the California Institute for Regenerative Medicine (CIRM) we are used to coming up with great ideas and hearing people ask “Well, how are you going to do that?”

Our new 5-year Strategic Plan is how. It’s the roadmap that will help guide us as we work to overcome critical bottlenecks in bringing regenerative medicine therapies to people in need.

Providing more than money

People often think of CIRM as a funding agency, providing the money needed to do research. That’s true, but it’s only part of the story. With every project we fund, we also offer a lot of support. That’s particularly true at the clinical stage, where therapies are being tested in people. Projects we fund in clinical trials don’t just get money, they also have access to:

  • Alpha Stem Cells Clinic Network – This is a group of specialized medical centers that have the experience and expertise to deliver new stem cell and gene therapies.
  • The CIRM Cell and Gene Therapy Center – This helps with developing projects, overcoming manufacturing problems, and offers guidance on working with the US Food and Drug Administration (FDA) to get permission to run clinical trials.
  • CIRM Clinical Advisory Panels (CAPs) – These are teams put together to help advise researchers on a clinical trial and to overcome problems. A crucial element of a CAP is a patient advocate who can help design a trial around the needs of the patients, to help with patient recruitment and retention.

Partnering with key stakeholders

Now, we want to build on this funding model to create new ways to support researchers in bringing their work to patients. This includes earlier engagement with regulators like the FDA to ensure that projects match their requirements. It includes meetings with insurers and other healthcare stakeholders, to make sure that if a treatment is approved, that people can get access to it and afford it.

In the past, some in the regenerative medicine field thought of the FDA as an obstacle to approval of their work. But as David Martin, a CIRM Board member and industry veteran says, the FDA is really a key ally.

“Turning a promising drug candidate into an approved therapy requires overcoming many bottlenecks… CIRM’s most effective and committed partner in accelerating this is the FDA.”

Removing barriers to manufacturing

Another key area highlighted in our Strategic Plan is overcoming manufacturing obstacles. Because these therapies are “living medicines” they are complex and costly to produce. There is often a shortage of skilled technicians to do the jobs that are needed, and the existing facilities may not be able to meet the demand for mass production once the FDA gives permission to start a clinical trial. 

To address all these issues CIRM wants to create a California Manufacturing Network that combines academic innovation and industry expertise to address critical manufacturing bottlenecks. It will also coordinate training programs to help build a diverse and expertly trained manufacturing workforce.

CIRM will work with academic institutions that already have their own manufacturing facilities (such as UC Davis) to help develop improved ways of producing therapies in sufficient quantities for research and clinical trials. The Manufacturing Network will also involve industry partners who can develop facilities capable of the large-scale production of therapies that will be needed when products are approved by the FDA for wider use.

CIRM, in collaboration with this network, will also help develop education and hands-on training programs for cell and gene therapy manufacturing at California community colleges and universities. By providing internships and certification programs we will help create a talented, diverse workforce that is equipped to meet the growing demands of the industry.

You can read more about these goals in our 2022-27 Strategic Plan.

Lack of diversity leaves cloud hanging over asthma drug study

Asthma spacer, photo courtesy Wiki Media Creative Commons

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If you want to know if a new drug or therapy is going to work in the people it affects the most you need to test the drug or therapy in the people most affected by the disease. That would seem blindingly obvious, wouldn’t it? Apparently not.

Case in point. A new asthma medication, one that seemingly shows real promise in reducing attacks in children, was tested on an almost entirely white patient population, even though Black and Puerto Rican children are far more likely to suffer from asthma.

The study enrolled more than 400 children, between the ages of 6 and 11, with moderate to serious uncontrolled asthma and treated them with a medication called Dupixent. The results, published in the New England Journal of Medicine, were impressive. Children given Dupixent had an average drop in severe asthma attacks of 65 percent compared to children given a placebo.

The only problem is 90 percent of the children in the study were white. Why is that a problem? Because, according to the Asthma and Allergy Foundation of America, only 9.5 percent of white children have asthma, compared to 24 percent of Puerto Rican children and 18 percent of Black children. So, the groups most likely to suffer from the disease were disproportionately excluded from a study about a treatment for the disease.

Some people might think, “So what! If the medication works for one kid it will work for another, what does race have to do with it?” Quite a lot actually.

A study in the Journal of Allergy and Clinical Immunology concluded that: “Race/ethnicity modified the association between total IgE (an antibody in the blood that is a marker for asthma) and asthma exacerbations. Elevated IgE level was associated with worse asthma outcomes in Puerto Ricans… Our findings suggest that eligibility for asthma biologic therapies differs across pediatric racial/ethnic populations.”

The article concluded by calling for “more studies in diverse populations for equitable treatment of minority patients with asthma.” Something that clearly didn’t happen in the Dupixent study.

While that’s more than disappointing, it’s not surprising. A recent study of vaccine clinical trials in JAMA Network Open found that:

  • Overall, white individuals made up almost 80 percent of people enrolled.
  • Black individuals were represented only 10.6 percent of the time.
  • Latino participants were represented just 11.6 percent of the time. 

Additionally, in pediatric trials, Black participants were represented just over 10 percent of the time and Latino participants were represented 22.5 percent of the time. The study concluded by saying that “diversity enrollment targets are needed for vaccine trials in the US.”

I would expand on that, saying they are needed for all clinical trials. That’s one of the many reasons why we at the California Institute for Regenerative Medicine (CIRM) are making Diversity, Equity and Inclusion an important part of everything we do, such as requiring all applicants to have a written DEI plan if they want funding from us. Dr. Maria Millan, our President and CEO, recently co-authored an article in Nature Cell Biology, driving home the need for greater diversity in basic science and research in general.

DEI has become an important part of the conversation this past year. But the Dupixent trial shows that if we are truly serious about making it part of what we do, we have to stop talking and start acting.

Stem Cell Agency Board Approves Roadmap for Next Five Years

Dr. Maria Millan, CIRM’s President & CEO

It’s hard to get somewhere if you don’t know where you are going. Without a map you can’t plan a route to your destination. That’s why the CIRM Board approved a new Strategic Plan laying out a roadmap for the Stem Cell Agency for the next five years.

The plan builds on the achievements of Proposition 71, the voter approved ballot initiative that created the Agency in 2004, including:

  • Supporting 76 clinical trials.
  • Helping cure more than 40 children born with a rare, fatal immune disorder.
  • Creating the Alpha Clinics Network that specializes in the delivery of stem cell therapies to patients.
  • Training over 3000 students and scholars to become the future workforce of regenerative medicine.
  • Stimulating California’s economy with $10.7 Billion in additional sales revenue and the creation of 56,000 new jobs (between 2004-2018)

The passage of Proposition 14 in 2020 has positioned CIRM to continue to accelerate research from discovery to clinical; to drive innovative, real-world solutions resulting in transformative treatments for patients; and to ensure the affordability and accessibility of those treatments to a diverse community of patients in an equitable manner, including those often overlooked or underrepresented in the past.

“We achieved a lot in the last 15 years and this provides a solid foundation for our strategy to bring us to the new era of CIRM and to deliver the full potential of regenerative medicine, says Dr. Maria T. Millan, the President and CEO of CIRM. “This plan lays out a roadmap for us to overcome the challenges in developing transformative therapies and making them accessible and affordable in an equitable fashion to a diverse California. The plan will guide us in that work through the development of novel scientific endeavors, effective healthcare delivery models, and expanded education and training programs.”

The Strategic Plan is organized into three main themes:

  • Advance World Class Science – Foster a culture of collaborative science by creating knowledge networks and shared research tools and technologies that encourage and facilitate data and resource sharing.
  • Deliver Real World Solutions – Accelerate approval of therapies by optimizing our support models for CIRM-funded clinical trials with attention to including underserved communities; build the California Manufacturing Network to overcome manufacturing hurdles; and expand the Alpha Clinics network and create the Community Care Centers of Excellence to deliver therapies to a diverse patient population often in underserved communities.
  • Provide Opportunity for All – Build a racially, ethnically and experientially diverse and highly skilled workforce to support the growing regenerative medicine economy in California; deliver a roadmap for access and affordability of regenerative medicine for all California patients.

Reflecting these goals, CIRM’s new mission statement is: Accelerating world class science to deliver transformative regenerative medicine treatments in an equitable manner to a diverse California and world.

“We realize that these are ambitious goals but they are achievable,” says Dr. Millan, “If CIRM is going to continue to be a global leader in the field of regenerative medicine, and to live up to the faith shown in us by the people of California, we believe we have to aim high. We have a terrific team, a clear vision and a determination to fulfill our mission. And that’s what we intend to do.”

Creating a New Model for Diversity in Scientific and Medical Research

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Nature Cell Biology cover

The global pandemic has highlighted many of the inequities in our health care system, with the virus hitting communities of color the hardest. That has led to calls for greater diversity, equity and inclusion at every level of scientific research and, ultimately, of medical care. A recently released article in the journal Nature Cell Biology, calls for “new models for basic and disease research that reflect diverse ancestral backgrounds and sex and ensure that diverse populations are included among donors and research participants.”

The authors of the article are Dr. Maria T. Millan, CIRM’s President & CEO; Rick Horwitz Senior Advisor and Executive Director, Emeritus, Allen Institute for Cell Science; Dr. Ekemini Riley, President, Coalition for Aligning Science; and Dr. Ruwanthi N. Gunawardane, Executive Director of the Allen Institute for Cell Science.

Dr. Maria Millan, CIRM’s President & CEO, says we need to make these issues a part of everything we do. “At CIRM we have incorporated the principles of promoting diversity, equity and inclusion in our research funding programs, education programs and future programs. We believe this is essential to ensure that the therapies our support helps advance will reach all patients in need and in particular communities that are disproportionately affected and/or under-served.”

The article highlights how, in addition to cultural, environmental, and socioeconomic factors, genetic factors also appear to play a role in the way disease affects different people. For example, 50 percent of people in South Asia have genetic traits that increases their risk for severe COVID-19, in contrast only 16 percent of Europeans have those traits.

But while some studies have shown how African American men are at greater risk for prostate cancer than white men, most of the research in this and other areas has been done on white populations of European ancestry. Efforts are already underway to change these disparities. For example, the National Institutes of Health (NIH) has sponsored the All of Us Research Program, which is inviting one million people across the U.S. to help build one of the most diverse health databases in history.

The article in Nature Cell Biology stresses the need to account for diversity at the individual molecular, cellular and tissue level. The authors make the point that diversity in those taking part in clinical trials is essential, but equally essential is that diverse biology is accounted for in the scientific work that leads to the development of potential therapies in order to increase the likelihood of success.

That’s why the authors of the article say: “If we are to truly understand human biology, address health disparities, and personalize our treatments, we need to go beyond our important, ongoing efforts in addressing diversity and inclusion in the workforce and the delivery of healthcare. We need to improve the data we generate by including diverse populations among donors and research participants. This will require new models and tools for basic and disease research that more closely reflect the diversity of human tissues, across diverse donor backgrounds.”

“Greater diversity in biological studies is not only the right thing to do, it is crucial to helping researchers make new discoveries that benefit everyone,” said Ru Gunawardane, Executive Director of the Allen Institute for Cell Science.

To do this they propose creating “a suite” of research cells, such as human induced pluripotent stem cell (hiPSC) lines from a diverse group of individuals to reflect the racial, ethnic and gender composition of the population. Human iPSCs are cells taken from any tissue (usually skin or blood) from a child or adult that have been genetically modified to behave like an embryonic stem cell. As the name implies, these cells are pluripotent, which means that they can become any type of adult cell.

CIRM has already created one version of what this suite would look like, through its iPSC Repository, a collection of more than 2,600 hiPSCs from individuals of diverse ancestries, including African, Hispanic, Native American, East and South Asian, and European. The Allen Institute for Cell Science also has a collection that could serve as a model for this kind of repository. Its collection of over 50 hiPSC

lines have been thoroughly analyzed on both a genomic and biological level and could also be broken down to include diversity in donor ethnicity and sex.

Currently researchers use cells from different lines and often follow very different procedures in using them, making it hard to compare results from one study to another. Having a diverse and well defined collection of research cells and cell models that are created by standardized procedures, could make it easier to compare results from different studies and share knowledge within the scientific community. By incorporating diversity in the very early stages of scientific research, the scientists and therapy developers gain a more complete picture of the biology disease and potential treatments.