Driving Innovation While Addressing Health Disparities Among People of Color

Image courtesy of Science Photo Library

One of the wonders of regenerative medicine is its broad applicability, which provides us with the opportunity to build upon existing knowledge and concepts.  In the midst of a global pandemic, researchers have responded to the needs of patients severely afflicted with COVID-19 by repurposing existing therapies being developed to treat patients.  The California Institute for Regenerative Medicine (CIRM) responded immediately to the pandemic and to researchers wanting to help by providing $5 million in emergency funding for COVID-19 related projects.  In a short time span, this funding has driven innovation in the form of 17 new projects targeting COVID-19, many of which are based on previously developed concepts being repurposed to deal with the novel coronavirus.

One such example is a clinical trial funded by CIRM that uses natural killer (NK) cells, a type of white blood cell that is a vital part of the immune system, which are administered to patients with COVID-19. NK cells play an important role in defense against cancer and in fighting off viral infections.  In fact, this exact same therapy was previously used in a clinical trial for patients with Acute Myeloid Leukemia, a type of blood cancer.

Another clinical trial funded by CIRM uses mesenchymal stromal cells (MSCs), a type of stem cell, to treat acute respiratory distress syndrome (ARDS), a life-threatening lung injury that occurs when fluid leaks into the lungs.  As a result of ARDS, oxygen cannot get into the body and patients have difficulty breathing.  ARDS is one of the most serious and lethal consequences of COVID-19, which is why this trial was expanded after the coronavirus pandemic to include COVID-19 positive patients.   

Despite these great strides in driving innovation of therapies, one challenge that still needs to be tackled is providing patients access to these therapies, particularly people from underrepresented and underserved communities.  In California alone, there have been over 621,000 positive cases as of August 2020, with more cases every day.  However, the impact of the pandemic is disproportionately affecting the Latinx and African American communities more than others. An analysis by the Los Angeles Times found that the Latinx and African American communities have double the mortality rate from the coronavirus in Los Angeles County.  Additionally, a surge in cases is being seen in poorer communities in comparison to wealthier ones.

Until a vaccine can be successfully developed and implemented to obtain herd immunity, the number of cases will continue to climb.  There is also the challenge of the long term health effects of COVID-19, which can consist of neurological, breathing, and heart problems according to an article in Science.  Unfortunately, a study published in the New England Journal of Medicine found that despite disproportionately higher rates of COVID-19 infection, hospitalization and death among people of color, they are significantly underrepresented in COVID-19 clinical trials.

The challenge of underrepresentation in clinical trials and research needs to be addressed by creating a more diverse population of study participants, so as to better generalize results to the U.S. population as a whole.  CIRM Board Member Ysabel Duron, a leading figure in cancer education in the Latinx community, has advocated for more inclusion and outreach efforts directed towards underserved and underrepresented communities.  By communicating with patients in underserved and underrepresented communities, building relationships established on a foundation of trust, and connecting patients with potential trial matches, underrepresentation can be alleviated.

To help in addressing these disparities, CIRM has taken action by changing the requirements for its discovery stage research projects, which promote promising new technologies that could be translated to enable broad use and improve patient care, and clinical trial stage projects.

For clinical trials, all proposals must include a written plan in the application for outreach and study participation by underserved and disproportionately affected populations. Priority will be given to projects with the highest quality plans in this regard. For discovery projects, all proposals must provide a statement describing how their overall study plan and design has considered the influence of race, ethnicity, sex and gender diversity.  Additionally, all proposals should discuss the limitations, advantages, and/or challenges in developing a product or tools that addresses the unmet medical needs of California’s diverse population, including underserved communities.  There is still much more work that needs to be done to address health disparities, but steps such as these can help steer progress in the right direction.

Driving innovation while addressing health disparities among people of color is just one of many opportunities and challenges of regenerative medicine in a post pandemic world.  This blog post is part of Signal’s fifth annual blog carnival. Please click here to read what other bloggers think about this topic.

Big time validation for early support

It’s not every day that a company and a concept that you helped support from the very beginning gets snapped up for $4.9 billion. But that’s what is happening with Forty Seven Inc. and their anti-cancer therapies. Gilead, another California company by the way, has announced it is buying Forty Seven Inc. for almost $5 billion.

The deal gives Gilead access to Forty Seven’s lead antibody therapy, magrolimab, which switches off CD47, a kind of “do not eat me” signal that cancer cells use to evade the immune system.

CIRM has supported this program from its very earliest stages, back in 2013, when it was a promising idea in need of funding. Last year we blogged about the progress it has made from a hopeful concept to an exciting therapy.

When Forty Seven Inc. went public in 2018, Dr. Irv Weissman, one of the founders of the company, attributed a lot of their success to CIRM’s support.

Dr. Irv Weissman

“The story of the funding of this work all of the way to its commercialization and the clinical trials reported in the New England Journal of Medicine is simply this: CIRM funding of a competitive grant took a mouse discovery of the CD47 ‘don’t eat me’ signal through all preclinical work to and through a phase 1 IND with the FDA. Our National Institutes of Health (NIH) did not fund any part of the clinical trial or preclinical run up to the trial, so it is fortunate for those patients and those that will follow, if the treatment continues its success in larger trials, that California voters took the state’s right action to fund research not funded by the federal government.”

Dr. Maria Millan, CIRM’s President & CEO, says the deal is a perfect example of CIRM’s value to the field of regenerative medicine and our ability to work with our grantees to make them as successful as possible.

“To say this is incredible would be an understatement! Words cannot describe how excited we are that this novel approach to battling currently untreatable malignancies has the prospect of making it to patients in need and this is a major step. Speaking on behalf of CIRM, we are very honored to have been a partner with Forty Seven Inc. from the very beginning.

CIRM Senior Science Officer, Dr. Ingrid Caras, was part of the team that helped a group of academic scientists take their work out of the lab and into the real world.

“I had the pleasure of working with and helping the Stanford team since CIRM provided the initial funding to translate the idea of developing CD47 blockade as a therapeutic approach. This was a team of superb scientists who we were fortunate to work closely with them to navigate the Regulatory environment and develop a therapeutic product. We were able to provide guidance as well as funding and assist in the ultimate success of this project.”

Forty Seven Inc. is far from the only example of this kind of support and collaboration. We have always seen ourselves as far more than just a funding agency. Money is important, absolutely. But so too is bringing the experience and expertise of our team to help academic scientists take a promising idea and turn it into a successful therapy.

After all that’s what our mission is, doing all we can to accelerate stem cell therapies to patients with unmet medical needs. And after a deal like this, Forty Seven Inc. is definitely accelerating its work.

CIRM-funded therapy helps “bubble babies” lead a normal life

Ja’Ceon Golden; ‘cured” of SCID

At CIRM we are very cautious about using the “c” word. Saying someone has been “cured” is a powerful statement but one that loses its meaning when over used or used inappropriately. However, in the case of a new study from U.C. San Francisco and St. Jude Children’s Research Hospital in Memphis, saying “cure” is not just accurate, it’s a celebration of something that would have seemed impossible just a few years ago.

The research focuses on children with a specific form of Severe Combined Immunodeficiency (SCID) called X-Linked SCID. It’s also known as “bubble baby” disease because children born with this condition lack a functioning immune system, so even a simple infection could be fatal and in the past they were kept inside sterile plastic bubbles to protect them.

In this study, published in the New England Journal of Medicine, researchers took blood stem cells from the child and, in the lab, genetically re-engineered them to correct the defective gene, and then infused them back into the child. Over time they multiplied and created a new blood supply, one free of the defect, which helped repair the immune system.

In a news release Dr. Ewelina Mamcarz, the lead author of the study, announced that ten children have been treated with this method.

“These patients are toddlers now, who are responding to vaccinations and have immune systems to make all immune cells they need for protection from infections as they explore the world and live normal lives. This is a first for patients with SCID-X1.”

The ten children were treated at both St. Jude and at UCSF and CIRM funded the UCSF arm of the clinical trial.

The story, not surprisingly, got a lot of attention in the media including this fine piece by CNN.

Oh, and by the way we are also funding three other clinical trials targeting different forms of SCID. One with UCLA’s Don Kohn,  one with Stanford’s Judy Shizuru, and one with UCSF’s Mort Cowan

Three people left blind by Florida clinic’s unproven stem cell therapy

Unproven treatment

Unproven stem cell treatments endanger patients: Photo courtesy Healthline

The report makes for chilling reading. Three women, all suffering from macular degeneration – the leading cause of vision loss in the US – went to a Florida clinic hoping that a stem cell therapy would save their eyesight. Instead, it caused all three to go blind.

The study, in the latest issue of the New England Journal of Medicine, is a warning to all patients about the dangers of getting unproven, unapproved stem cell therapies.

In this case, the clinic took fat and blood from the patient, put the samples through a centrifuge to concentrate the stem cells, mixed them together and then injected them into the back of the woman’s eyes. In each case they injected this mixture into both eyes.

Irreparable harm

Within days the women, who ranged in age from 72 to 88, began to experience severe side effects including bleeding in the eye, detached retinas, and vision loss. The women got expert treatment at specialist eye centers to try and undo the damage done by the clinic, but it was too late. They are now blind with little hope for regaining their eyesight.

In a news release Thomas Alibini, one of the lead authors of the study, says clinics like this prey on vulnerable people:

“There’s a lot of hope for stem cells, and these types of clinics appeal to patients desperate for care who hope that stem cells are going to be the answer, but in this case these women participated in a clinical enterprise that was off-the-charts dangerous.”

Warning signs

So what went wrong? The researchers say this clinic’s approach raised a number of “red flags”:

  • First there is almost no evidence that the fat/blood stem cell combination the clinic used could help repair the photoreceptor cells in the eye that are attacked in macular degeneration.
  • The clinic charged the women $5,000 for the procedure. Usually in FDA-approved trials the clinical trial sponsor will cover the cost of the therapy being tested.
  • Both eyes were injected at the same time. Most clinical trials would only treat one eye at a time and allow up to 30 days between patients to ensure the approach was safe.
  • Even though the treatment was listed on the clinicaltrials.gov website there is no evidence that this was part of a clinical trial, and certainly not one approved by the Food and Drug Administration (FDA) which regulates stem cell therapies.

As CIRM’s Abla Creasey told the San Francisco Chronicle’s Erin Allday, there is little evidence these fat stem cells are effective, or even safe, for eye conditions.

“There’s no doubt there are some stem cells in fat. As to whether they are the right cells to be put into the eye, that’s a different question. The misuse of stem cells in the wrong locations, using the wrong stem cells, is going to lead to bad outcomes.”

The study points out that not all projects listed on the Clinicaltrials.gov site are checked to make sure they are scientifically sound and have done the preclinical testing needed to reduce the likelihood they may endanger patients.

goldberg-jeffrey

Jeffrey Goldberg

Jeffrey Goldberg, a professor of Ophthalmology at Stanford and the co-author of the study, says this is a warning to all patients considering unproven stem cell therapies:

“There is a lot of very well-founded evidence for the positive potential of stem therapy for many human diseases, but there’s no excuse for not designing a trial properly and basing it on preclinical research.”

There are a number of resources available to people considering being part of a clinical trial including CIRM’s “So You Want to Participate in a Clinical Trial”  and the  website A Closer Look at Stem Cells , which is sponsored by the International Society for Stem Cell Research (ISSCR).

CIRM is currently funding two clinical trials aimed at helping people with vision loss. One is Dr. Mark Humayun’s research on macular degeneration – the same disease these women had – and the other is Dr. Henry Klassen’s research into retinitis pigmentosa. Both these projects have been approved by the FDA showing they have done all the testing required to try and ensure they are safe in people.

In the past this blog has been a vocal critic of the FDA and the lengthy and cumbersome approval process for stem cell clinical trials. We have, and still do, advocate for a more efficient process. But this study is a powerful reminder that we need safeguards to protect patients, that any therapy being tested in people needs to have undergone rigorous testing to reduce the likelihood it may endanger them.

These three women paid $5,000 for their treatment. But the final cost was far greater. We never want to see that happen to anyone ever again.