Battling COVID and turning back the clock on stem cell funding

Coronavirus

Battling the virus that causes COVID-19 is something that is top of everyone’s mind right now. That’s why CIRM is funding 17 different projects targeting the virus. But one of the most valuable tools in helping develop vaccines against a wide variety of diseases in the past is now coming under threat. We’ll talk about both issues in a live broadcast we’re holding on Wednesday, October 14th at noon (PDT).

That date is significant because it’s Stem Cell Awareness Day and we thought it appropriate to host a meeting looking at two of the most important issues facing the field.

The first part of the event will focus on the 17 projects that CIRM is funding that target COVID-19. This includes three clinical trials aiming to treat people who have been infected with the virus and are experiencing some of the more severe effects, such as damaged lungs.

We’ll also look at some of the earlier stage research that includes:

  • Work to help develop a vaccine
  • Using muscle stem cells to help repair damage to the diaphragm in patients who have spent an extended period on a ventilator
  • Boosting immune system cells to help fight the virus

The second part of the event will look at ways that funding for stem cell research at the federal level is once again coming into question. The federal government has already imposed new restrictions on funding for fetal tissue research, and now there are efforts in Congress to restrict funding for embryonic stem cell research.

The impacts could be significant. Fetal tissue has been used for decades to help develop some of the most important vaccines used today including rubella, chickenpox, hepatitis A, and shingles. They have also been used to make approved drugs against diseases including hemophilia, rheumatoid arthritis, and cystic fibrosis.

We’ll look at some of the reasons why we are seeing these potential restrictions on the medical research and what impact they could have on the ability to develop new treatments for the coronavirus and other deadly diseases.

You can watch the CIRM Stem Cell Awareness Day live event by going here: https://www.youtube.com/c/CIRMTV/videos at noon on Wednesday, October 14th.

Feel free to share news about this event with anyone you think might be interested.

We look forward to seeing you there.

CIRM Board Approves Two Additional COVID-19 Projects

Dr. Vaithilingaraja Arumugaswami (left) and Dr. Song Li (right), UCLA

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved two additional projects as part of the $5 million in emergency funding for COVID-19 related projects. This brings the number of projects CIRM is supporting to 11, including two clinical trials.

The Board awarded $349,999 to Dr. Vaithilingaraja Arumugaswami at UCLA.  The focus of this project will be to study Berzosertib, a therapy targeting viral replication and damage in lung stem cells.  The ultimate goal would be to use this agent as a therapy to prevent COVID-19 viral replication in the lungs, thereby reducing lung injury, inflammation, and subsequent lung disease caused by the virus.  

This award is part of CIRM’s Translational Stage Research Program (TRAN1), which promotes the activities necessary for advancement to clinical study of a potential therapy.

The Board also awarded $149,916 to Dr. Song Li at UCLA.  This project will focus on developing an injectable biomaterial that can induce the formation of T memory stem cells (TMSCs), an important type of stem cell that plays a critical role in generating an immune response to combat viruses. In vaccine development, there is a major challenge that the elderly may not be able to mount a strong enough immunity.  This innovative approach seeks to address this challenge by increasing TMSCs in order to boost the immune response to vaccines against COVID-19.

This award is under CIRM’s Discovery Stage Research Program (DISC2), which promotes promising new technologies that could be translated to enable broad use and improve patient care.

“CIRM continues to support novel COVID-19 projects that build on previous knowledge acquired,” says Dr. Maria T. Millan, the President & CEO of CIRM. “These two projects represent the much-needed multi-pronged approach to the COVID-19 crisis, one addressing the need for effective vaccines to prevent disease and the other to treat the severe illness resulting from infection.”

Stem Cell Agency Board Approves Three More Projects Targeting COVID-19

Dr. Jianhua Yu (left), Dr. Helen Blau (center), and Dr. Albert Wong (right)

The COVID-19 virus targets many different parts of the body, often with deadly or life-threatening consequences. This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved investments in three early-stage research programs taking different approaches to battling the virus.

Dr. Jianhua Yu at the Beckman Research Institute of City of Hope was awarded $150,000 to use stem cells from umbilical cord blood to attack the virus. Dr. Yu and his team have many years of experience in taking cord blood cells and turning them into what are called chimeric antigen receptor (CAR) natural killer (NK) cells. The goal is to deploy these CAR NK cells to specifically target cells infected with COVID-19. This leverages the body of work at the City of Hope to develop this technology for cancer.

Dr. Helen Blau of Stanford University was awarded $149,996 to target recovery of muscle stem cells of the diaphragm in COVID-19 patients who have an extended period on a ventilator.

Patients with severe coronavirus often suffer respiratory failure and end up on mechanical ventilation that takes over the work of breathing. Over time, the diaphragm, the main muscle responsible for inhaling and exhaling, weakens and atrophies. There is no treatment for this kind of localized muscle wasting and it is anticipated that some of these patients will take months, if not years, to fully recover. Dr. Blau’s team proposes to develop a therapy with Prostaglandin E2 and Bupivacaine based on data generated by Dr. Blau’s group that these drugs, already approved by the FDA for other indications, have the potential to stimulate muscle stem cell recovery.

Dr. Albert Wong, also from Stanford University, was awarded $149,999 to develop vaccine candidates against COVID-19.

Most vaccine candidates are focused on getting the body to produce an antibody response to block the virus. However, Dr. Wong thinks that to be truly effective, a vaccine also needs to produce a CD8+ T cell response to augment an effective immune response to remove the COVID-19 infected cells that are hijacked by the virus to spread and cause illness.  This team will use the experience it gained using CIRM funds to vaccine against glioblastoma, a deadly brain cancer, to advance a similar approach to produce an effective cellular immune response to combat COVID-19.  

“CIRM is committed to supporting novel, multi-pronged approaches to battle this COVID-19 crisis that leverage solid science and knowledge gained in other areas.” says Dr. Maria T. Millan, the President & CEO of CIRM. “These three projects highlight three very different approaches to combatting the acute devastating health manifestations of COVID-19 as well as the debilitating sequelae that impact the ability to recover from the acute illness. Through this COVID funding opportunity, CIRM is enabling researchers to re-direct work they have already done, often with CIRM support, to quickly develop new approaches to COVID-19.”

CIRM Board Expands Efforts of COVID-19 Program

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) expanded efforts related to the $5 million in emergency funding for the CIRM COVID-19 program.

The new guidelines mean that inception discovery projects (DISC1), whose goal is developing new and transformational ideas, will now be eligible for CIRM COVID-19 funding.  These projects can receive up to $150,000 and must have data to confirm or reject their hypothesis within 6 months. In addition to this, quest discovery projects (DISC2), which promote the discovery of new technologies that could be translated to enable broad use, can now receive up to $250,000 in funding.

The Board approved using $1 million from the program in supplemental support for CIRM-funded COVID-19 clinical trials. Under the change an existing clinical trial can receive up to $250,000 in additional funding but must demonstrate sufficient progress and specific activities in order to be eligible.  The Board will also require that all clinical trial projects include a plan for outreach and study participation by underserved and disproportionately affected populations.

The Board also strongly encouraged those that meet the stem cell component for vaccine development for COVID-19 to apply for funding.

“We continue to receive large amounts of inquiries and applications to the COVID-19 program announcement,” said Maria T. Millan, M.D., President and CEO of CIRM. “The amendments passed by our Board today will provide additional opportunities for CIRM to support novel vaccine development, fundamental discoveries and the acceleration of clinical programs.”

A New Vaccine Could Make Stem Cell Transplants Safer

Stem cell transplants offer a lot of promise for treating or curing patients who’ve exhausted their therapeutic options. However, there are some potential risks associated with putting stem cells into the human body such as cancer and infection. But scientists and clinicians are working hard to reduce the risk of stem cell therapies by testing them in animals and in early stage clinical trials.

There was good news recently when scientists at the City of Hope reported that they’ve developed a vaccine that could make stem cell transplants safer.

Cytomegalovirus. Image credit (https://scienceforscientists.wordpress.com/tag/cytomegalovirus-cmv/)

Cytomegalovirus. Image credit scienceforscientists

The vaccine helps the immune system fight cytomegalovirus (CMV), which affects 50-80% of adults in the US. CMV typically lies dormant in the human body, but it can be activated in immunocompromised people, pregnant women, and patients receiving stem cell transplants. Once activated, CMV can cause nasty infections and even hepatitis (liver inflammation). There are anti-viral drugs that patients suffering from CMV flare-ups can take, but these drugs are very toxic and can sometimes do more harm than good.

CMVPepVax to the rescue!

In a report published in the Lancet Haematology, the group at City of Hope described a CMV vaccine called CMVPepVax that’s both safe and effective in protecting patients receiving stem cell transplants from CMV flare-ups. They tested the vaccine in a phase 1 clinical trial in 36 patients receiving stem cell treatments for cancer or other diseases. Half of the group received two doses of the vaccine at different time points (28 and 56 days), and the other half didn’t get the vaccine.

After three months, the researchers compared the group that received the vaccine to the control group and saw striking differences. Patients who got CMVPepVax had a boosted immune response against CMV, lower occurrence of CMV flare-ups, and reduced need for anti-viral drugs.

First author on the study, Ryotaro Nakamura, commented:

Ryotaro Nakamura

Ryotaro Nakamura

“Overall, people who received the vaccine had more robust immune recovery than those in the observation group. I was surprised because I didn’t expect to see such a dramatic difference between the two groups in such a small sample study.”

 

But wait, there’s more good news!

Even more exciting was the observation that patients receiving the vaccine were less likely to experience a relapse of their disease (leukemia was given as an example) and had a lower risk of death.

Senior author on the paper Don Diamond explained,

Don Diamond

Don Diamond

“We didn’t anticipate this to happen. Yet we found this striking signal from the data, which told us that those in the vaccine arm of the trial were less likely to relapse of their disease and less likely to develop problems that would lead to non-relapse mortality. In the future, the CMVPepVax vaccine may prove useful not only for patients receiving stem cell transplants, but also for recipients of solid organ transplants or other immunodeficiency diseases.”

Hold your horses

Of course, with any exciting breakthrough such as this, it’s wise to not count your chickens too early. In a City of Hope press release, both Nakamura and Diamond said that these results need to be replicated in a larger phase 2 trial before they can conclude that the vaccine works.

The trial is currently underway. It’s a larger, double-blind study that will compare patients receiving CMVPepVax to a placebo group. It’s the authors’ hope that the results from this trial will support their earlier phase 1 results and also shed light on why the vaccine protects against leukemia relapse.

Diamond concluded:

“We want to get confirmation to see whether lightning strikes twice with these effects. The current phase 2 trial, funded by the National Cancer Institute, will tell us whether the protective effects are really valid. If they are, it would be quite exciting.”

 

The results of this phase 2 trial will be especially important given the recent news about the failure of Chimerix Inc.’s antiviral CMV drug. The company’s stock took a huge hit today after they reported that their oral antiviral CMV drug didn’t reduce infection in stem cell transplant patients in a late-stage study.

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