Month: April 2020

Stem Cells for Parkinson’s Disease

/ Kevin McCormack / Leave a comment

While the world has been turned upside down by the coronavirus pandemic, the virus poses an increased threat to people with Parkinson’s disease (PD). Having a compromised immune system, particularly involving the lungs, means people with PD are at higher risk of some of the more dangerous complications of COVID-19. So, this seems like an appropriate time for CIRM to hold a special Facebook Live “Ask the Stem Cell Team” About Parkinson’s disease.

We are holding the event on Tuesday, May 5th at noon PDT.

The initial reason for the Facebook Live was the CIRM Board approving almost $8 million for Dr. Krystof Bankiewicz at Brain Neurotherapy Bio, Inc. to run a Phase 1 clinical trial targeting PD. Dr. Bankiewicz is using a gene therapy approach to promote the production of a protein called GDNF, which is best known for its ability to protect dopaminergic neurons, the kind of cell damaged by Parkinson’s. The approach seeks to increase dopamine production in the brain, alleviating PD symptoms and potentially slowing down the disease progress.

Dr. Bankiewicz will be joined by two of CIRM’s fine Science Officers, Dr. Lila Collins and Dr. Kent Fitzgerald. They’ll talk about the research targeting Parkinson’s that CIRM is funding plus other promising research taking place.

And we are delighted to have a late addition to the team. Our CIRM Board member and patient advocate for Parkinson’s disease, Dr. David Higgins. David has a long history of advocacy for PD and adds the invaluable perspective of someone living with PD.

As always, we want this to be as interactive as possible, so we want to get your questions. You can do this on the day, posting them alongside the live feed, or you can send them to us ahead of time at info@cirm.ca.gov. We’ll do our best to answer as many as we can on the day, and those we don’t get to during the broadcast we’ll answer in a later blog.

We look forward to seeing you there.

Two UCLA scientists receive CIRM funding for discovery research for COVID-19

/ Yimy Villa / Leave a comment
Dr. Brigitte Gomperts (left) and Dr. Gay Crooks (right), UCLA
Image Credit: UCLA Broad Stem Cell Center

This past Friday, the CIRM Board approved funding for its first clinical study for COVID-19. In addition to this, the Board also approved two discovery stage research projects, which support promising new technologies that could be translated to enable broad use and improve patient care. Before we go into more detail, the two awards are summarized in the table below:

The discovery grant for $150,000 was given to Dr. Gay Crooks at UCLA to study how specific immune cells called T cells respond to COVID-19. The goal of this is to inform the development of vaccines and therapies that harness T cells to fight the virus. Typically, vaccine research involves studying the immune response using cells taken from infected people. However, Dr. Crooks and her team are taking T cells from healthy people and using them to mount strong immune responses to parts of the virus in the lab. They will then study the T cells’ responses in order to better understand how T cells recognize and eliminate the virus.

This method uses blood forming stem cells and then converts them into specialized immune cells called dendritic cells, which are able to devour proteins from viruses and chop them into fragments, triggering an immune response to the virus.

In a press release from UCLA, Dr. Crooks says that, “The dendritic cells we are able to make using this process are really good at chopping up the virus, and therefore eliciting a strong immune response”

The discovery grant for $149,998 was given to Dr. Brigitte Gomberts at UCLA to study a lung organoid model made from human stem cells in order to identify drugs that can reduce the number of infected cells and prevent damage in the lungs of patients with COVID-19. Dr. Gomberts will be testing drugs that have been approved by the U.S. Food and Drug Administration (FDA) for other purposes or have been found to be safe in humans in early clinical trials. This increases the likelihood that if a successful drug is found, it can be approved more rapidly for widespread use.

In the same press release from UCLA, Dr. Gomberts discusses the potential drugs they are evaluating.

“We’re starting with drugs that have already been tested in humans because our goal is to find a therapy that can treat patients with COVID-19 as soon as possible.”

CIRM Board Funds its First Clinical Study for COVID-19

/ Yimy Villa / 1 Comment
Dr. John Zaia, City of hope

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) continued its commitment to help with the coronavirus pandemic by awarding $749,999 to Dr. John Zaia at City of Hope.  He will be conducting a clinical study to administer blood plasma from recovered COVID-19 patients to treat those with the virus.  This marks CIRM’s first clinical study for COVID-19 after approving emergency funding a month earlier.

Plasma is a component of blood that carries proteins called antibodies that are usually involved in defending our bodies against viral infections.  Blood plasma from patients that have recovered from COVID-19, referred to as convalescent plasma, contain antibodies against the virus that can be used as a potential treatment for COVID-19.  Currently, there are challenges with this approach that include: properly identifying convalescent plasma donors i.e. recovered patients, determining eligibility of those with convalescent plasma that want to donate, collection of the plasma, treating patients, and determining if the plasma was effective.

Dr. Zaia and his team at City of Hope will create the COVID-19 Coordination Program, which addresses solutions for all of the challenges listed above. The program will partner with the medical teams at CIRM’s Alpha Stem Cell Clinic Network, as well as infectious disease, pulmonary and critical care teams from medical centers and community hospitals across the state.  Potential donors will be identified and thoroughly screened for eligibility per the established National and State blood banking safety requirements. Finally, the convalescent plasma will be collected from eligible donors and administered by licensed physicians to COVID-19 patients, who will be evaluated for response to the treatment and potential recovery.

“We are in the midst of very challenging times where there is not yet an approved treatment for COVID-19. In response to this, CIRM launched and executed an emergency COVID-19 funding program, which was made possible by our Board, patient advocates, California scientists, external scientific expert reviewers, and our dedicated team,” said Maria T. Millan, MD, President and CEO of CIRM. “With CIRM funding, the City of Hope COVID-19 Coordination program will tap into CIRM’s network of researchers, physicians, and our Alpha Clinics to deliver this treatment to patients in need.  It will also serve the critical role of gathering important scientific data about the plasma, safety, and clinical data from treated patients.”

The Board also approved a discovery stage research project that utilizes stem cell models for a novel approach to vaccine development against the virus causing COVID-19 and another project that uses a unique lung stem cell organoid to identify an effective drug against the virus.

The two awards are summarized in the table below:

Helping the blind see – mice that is

/ Kevin McCormack / Leave a comment

When I first saw the headline for this story I thought of the nursery rhyme about the three blind mice. Finally, they’ll be able to see the farmer’s wife coming at them with a carving knife. But the real-world implications are of this are actually pretty exciting.

Researchers at the National Institute of Health’s National Eye Institute took skin cells from mice and directly reprogrammed them into becoming light sensitizing cells in the eye, the kind that are often damaged and destroyed by diseases like macular degeneration or retinitis pigmentosa.

What’s particularly interesting about this is that it bypassed the induced pluripotent stem cell (iPSC) stage where researchers turn the skin cells into embryonic-like cells, then turn those into the cells found in the eye.

In a news release, Anand Swaroop of the NEI says this more direct approach has a number of advantages: “This is the first study to show that direct, chemical reprogramming can produce retinal-like cells, which gives us a new and faster strategy for developing therapies for age-related macular degeneration and other retinal disorders caused by the loss of photoreceptors.”

After converting the skin cells into cells called rod photoreceptors – the light sensing cells found in the back of the eye – the team transplanted them into blind mice. One month later they tested the mice to see if there had been any change in vision. There had; 43 percent of the mice reacted to light exposure, something they hadn’t done before.

Biraj Mahato, the study’s first author, said that three months later, the transplanted cells were still alive and functioning. “Even mice with severely advanced retinal degeneration, with little chance of having living photoreceptors remaining, responded to transplantation. Such findings suggest that the observed improvements were due to the lab-made photoreceptors rather than to an ancillary effect that supported the health of the host’s existing photoreceptors.”

Obviously there is a lot of work still to do before we can even begin to think about trying something like this in people. But this is certainly an encouraging start.

In the meantime, CIRM is funding a number of stem cell programs aimed at treating vision destroying diseases like macular degeneration and retinitis pigmentosa.

Stem cell clinical trial for COVID-19 patients gets emergency federal approval

/ Yimy Villa / Leave a comment
Dr. Camillo Ricordi, principal investigator of a stem cell trial for COVID-19 at the
University of Miami Miller School of Medicine
Image Credit: Diabetes Research Institute Foundation Website

A team of doctors at the University of Miami (UM) Miller School of Medicine received emergency approval from the U.S. Food and Drug Administration (FDA) to conduct a clinical trial to treat patients with severe lung inflammation as a result of COVID-19.

The doctors will use stem cells obtained from umbilical cord blood and will deliver them via intravenous (IV) infusion to 12 patients. IV infusions of stem cells are known to travel directly to the lungs, the location where damage is being caused in severe cases of COVID-19. When a patient contracts the virus, their body produces cytokines, proteins that play an important role in the immune response. Unfortunately, having too many cytokines, known as a “cytokine storm”, leads to a severe immune reaction which causes damage to the lungs.

Umbilical cord stem cells are known to contain anti-inflammatory properties and the UM team hopes that the treatment can alleviate the “cytokine storm” and lung inflammation. The rationale for this approach is based off of a small study in China where seven patients received this treatment and showed improvement in lung function and symptoms. Despite these positive results, it is important to note that this trial is in very early testing and will need to demonstrate significant improvement in larger patient groups.

In an article from the Miami Herald, Dr. Camillo Ricordi, principal investigator of the trial, discusses how the results of the therapy will be observed very quickly if successful.

“This is not a study you have to follow up with in six months, because the results are immediate. In one week, you know: Is it working or not?”

In the same article from the Miami Herald, Dr. Ricordi discusses how the team of UM researchers and doctors are preparing to expand the trial to more patients if it is successful.

“We are already doing cell production anticipating this. We are planning for success, but of course we have to see how it does with our patients.”

Living proof science can find a cure

/ Kevin McCormack / 2 Comments

Like many kids, let’s face it, many adults too, Ronav “Ronnie” Kashyap is getting a little bored stuck inside all day during the coronavirus pandemic. This video, shot by his dad Pawash, shows Ronnie trying to amuse himself by pretending to be hard at work.

https://www.instagram.com/p/B_BSQaonFXb/

It’s a lovely moment. It’s also a moment that just a few years ago seemed almost impossible. That’s because Ronnie was born with severe combined immunodeficiency (SCID). SCID kids have no functioning immune system so even a simple infection, such as a cold, can be life-threatening.

Many of those hardest hit by COVID-19 have compromised immune systems. But try fighting the virus if you have no immune system at all. The odds would not be good.

Happily, we don’t have to imagine it because Ronnie is one of around 60 children who have undergone CIRM-supported stem cell/gene therapies that have helped repair their immune system.

In Ronnie’s case he was rushed to UC San Francisco shortly after his birth when a newborn screening test showed he had SCID. He spent the next several months there, in isolation with his parents, preparing for the test. Doctors took his own blood stem cells and, in the lab, corrected the genetic mutation that causes SCID. The cells were then re-infused into Ronnie where they created a new blood supply and repaired his immune system.

How good is his immune system today? Last year his parents, Upasana and Pawash, were concerned about taking Ronnie to a crowded shopping mall for fear he might catch a cold. Their doctor reassured them that he would be fine. So, they went. The doctor was right, Ronnie was fine. However, Upasana and Pawash both caught colds!

Just a few weeks ago Ronnie started pre-school. He loves it. He loves having other kids to play with and his parents love it because it helps him burn off some energy. But they also love it because it showed Ronnie is now leading a normal life, one where they don’t have to worry about everything he does, every person he comes into contact with.

Sounds a bit like how the rest of us are living right now doesn’t it. And the fears that Ronnie’s parents had, that even a casual contact with a friend, a family member or stranger, might prove life-threatening, are ones many of us are experiencing now.

When Ronnie was born he faced long odds. At the time there were only a handful of scientists working to find treatments for SCID. But they succeeded. Now, Ronnie, and all the other children who have been helped by this therapy are living proof that good science can overcome daunting odds to find treatments, and even cures, for the most life-threatening of conditions.

Today there are thousands, probably tens of thousands of scientists around the world searching for treatments and cures for COVID-19. And they will succeed.

Till then the rest of us will have to be like Ronnie. Stay at home, stay safe, and enjoy the luxury of being bored.

Study shows that exercise rejuvenates muscle stem cells of old mice

/ Yimy Villa / 3 Comments
Dr. Thomas Rando, Stanford University

While we’re all at home and practicing social distancing during this global pandemic, it has become a challenge to get in daily exercise. Aside from outward physical appearance, what other benefits does exercise hold? Dr. Thomas Rando and his team at Stanford University explored this question in more detail in a CIRM supported animal study.

The Stanford research team found that exercise played a key role in restoring the youthful properties in the muscle stem cells of old mice. Muscle stem cells play an important role in tissue regeneration. They are usually on standby alongside muscle fibers in a resting state known as quiescence until called upon to repair damage.

For this study, the researchers wanted to see if voluntary exercise had an effect on the muscle stem cells in mice. Older mice that were 20 months old, the equivalent of 60-70 human years, were given an exercise wheel where they were allowed to run at will. Younger mice that were 3-4 months old, the equivalent of 20-30 human years, were also given an exercise wheel and allowed to run at will. A separate group of younger and older mice were given a wheel that didn’t rotate to compare them with the groups of mice that exercised.

They found that the older animals that had exercised regularly were significantly better at repairing muscle damage compared to their counterparts that did not exercise. However, this exercise benefit was not observed between the younger group of mice.

The researchers also transplanted the muscle stem cells from the older mice that had exercised into younger mice that had not exercised. They found that the muscle stem cells from the older mice contributed more to the repair process than did those from the non-exercising mice.

What was also surprising is that injecting blood from an old mouse that had exercised into an old mouse that hadn’t created a similar benefit in the muscle stem cells. This finding suggests that exercise simulates the production of some factors that then circulate in the blood and enhance the function of older stem cells.

Lastly, the researchers were ably to identify a molecular pathway that activates the resting muscle stem cells in response to damage.

In a press release, Dr. Rando discusses how this discovery could potentially lead to the development of a drug that could rejuvenate muscle stem cells.

“If we could develop a drug that mimics this effect, we may be able to experience the benefit without having to do months of exercise.”

The full results of this study were published in Nature Metabolism.

CIRM Board Expands COVID-19 Efforts

/ Yimy Villa / Leave a comment
Coronavirus particles, illustration. Courtesy KTSDesign/Science Photo Library

This past Friday, the governing Board of the California Institute for Regenerative Medicine (CIRM) expanded the eligibility criteria for COVID-19 related projects to develop new treatments against the virus.  Just two weeks ago, the Board approved $5 million in emergency funding for COVID-19 research.

One major addition is allowing research related to convalescent plasma to be eligible for CIRM COVID-19 emergency funding.  Plasma is a component of blood that carries cells and antibodies.  Blood plasma from patients that have recovered from COVID-19, referred to as convalescent plasma, contains antibodies against the virus and could be used as a potential treatment for COVID-19 patients.

In addition to this, potential clinical studies of convalescent plasma are now approved for use by the U.S. Food and Drug Administration (FDA) single-patient emergency Investigational New Drug (eIND) pathway as opposed to only a traditional IND.  Before treatments can be tested in humans, a traditional IND needs to be filed.  In an emergency situation such as the coronavirus pandemic, an eIND can be filed to begin testing the treatment faster.

In order to address the disproportionate impact of COVID-19 on underserved communities, priority will be given to projects that directly address these disparities. 

Lastly, potential clinical programs for COVID-19 are now approved to start incurring allowable project costs, at risk, from the date of the application submission deadline.  This would give researchers the opportunity to start their projects earlier and cover project costs retroactively if they are approved for funding.

“The intent behind this amendment is to be responsive to this COVID-19 crisis by leveraging CIRM’s funding programs, processes, and infrastructure within the scientific ecosystem that it has supported to date,” said Maria T. Millan, M.D., President and CEO of CIRM. “By providing an opportunity for the medical and scientific community to gather important data while using convalescent plasma treatment protocols on an emergency basis, CIRM is joining the global effort to expedite treatments to patients in need in the midst of this global pandemic.”

CIRM has established an open call for proposals and will accept applications on a bi-monthly basis.

Please refer to the following Program Announcement for more details:

·      Special Call for COVID-19 Projects

To Submit an Application:

  1. Go to the Grants Management Portal (https://grants.cirm.ca.gov) and log in with your existing CIRM Username and Password. If you do not have a Username, Click on the “New User” link and follow the instructions to create a CIRM Username and password.
  2. After logging in, click on the Menu tab. Select the tab labeled “Open Programs“. Under the section labeled “RFAs and Programs Open for Applications“, click on the “Start a Grant Application” link for your selected program.
  3. Complete each section of the Application by clicking on the appropriate link and following the posted instructions. Proposal templates can be located and submitted under the “Uploads” section.
  4. To submit your Application, click on the “Done with Application” button. The “Done with Application” button will be enabled when all of the mandatory sections have been completed. Please note that once this has been selected, you will no longer be able to make changes to your Application.
  5. To confirm submission of your Application, select the tab labeled “Your Applications” and check the table under the section labeled “Your Submitted Applications“. You will see your Application number and project title listed once the submission process has been completed.

Cashing in on COVID-19

/ Kevin McCormack / Leave a comment
Coronavirus particles, illustration. Courtesy KTSDesign/Science Photo Library

As the coronavirus pandemic continues to spread, one of the few bright spots is how many researchers are stepping up and trying to find new ways to tackle it, to treat it and hopefully even cure it. Unfortunately, there are also those who are simply trying to cash in on it.

In the last few years the number of predatory clinics offering so-called “stem cell therapies” for everything from Alzheimer’s and multiple sclerosis to autism and arthritis has exploded in the US. The products they offer have not undergone a clinical trial to show that they work; they haven’t been approved by the US Food and Drug Administration (FDA); they don’t have any evidence they are even safe. But that doesn’t stop them marketing these claims and it isn’t stopping some of them from now trying to cash in on the fears created by the coronavirus.

One company is hawking what it calls a rapid COVID-19 test, one that can determine if you have the virus in under ten minutes (many current tests take days to produce a result). All it takes is a few drops of blood and, from the comfort of your own home, you get to find out if you are positive for COVID-19. And best of all, it claims it is 99 percent accurate.

What could be the problem with that? A lot as it turns out.

If you go to the bottom of the page on the website marketing the test it basically says “this does not work and we’re not making any claims or are in any way responsible for any results it produces.” So much for 99 percent accurate.

It’s not the only example of this kind of shameless attempt to cash in on COVID-19. So it’s appropriate that this week the Alliance for Regenerative Medicine (ARM), issued a statement strongly condemning these attempts and the clinics behind them.

ARM warns about the growing number of “stem cell clinics” (that) are taking advantage of the “hype” around stem cells – and, in certain cases, the current concern about COVID-19 – and avoiding regulation by falsely marketing illegal and potentially harmful products to patients seeking cures.” 

These so called “therapies” or tests do more than just take money – in some cases tens of thousands of dollars – from individuals: “Public health is at risk when unscrupulous providers offer stem cell products that are unapproved, unproven and fail to adhere to established rules for good manufacturing practices. Many of these providers put patients at risk by falsely marketing the benefits of treatments, and often promoting the stem cells for conditions that are outside of their area of medical expertise.”

It’s sad that even in times when so many people are working hard to find treatments for the virus, and many are risking their lives caring for those who have the virus, that there are unscrupulous people trying to make money out of it. All we can do is be mindful, be careful and be suspicious of anything that sounds too good to be true.

There are no miracle cures. No miracle treatments. No rapid blood tests you can order in the mail. Be aware. And most importantly of all, be safe.

The CIRM Board recently held a meeting to approve $5 million in emergency funding for rapid research into potential treatments for COVID-19.

Novel clinical trial for COVID-19 using immune cells

/ Yimy Villa / 1 Comment
This scanning electron microscope image shows SARS-CoV-2 (yellow)—also known as 2019-nCoV, the virus that causes COVID-19—isolated from a patient in the U.S., emerging from the surface of cells (blue/pink) cultured in the lab.
Image Credit: National Institute of Allergy and Infectious Diseases–Rocky Mountain Laboratories

During this global pandemic, many scientists are pursuing various avenues for potential treatments of COVID-19.  The Infectious Disease Research Institute (IDRI), in collaboration with Celularity Inc., will conduct a clinical trial with 100 patients using an immunotherapy for treatment of COVID-19.

The treatment will involve administering specialized immune cells called Natural Killer (NK) cells, which are a type of white blood cell that are a vital part of the immune system. Previously, these cells have been administered in early safety studies to treat patients with blood cancers. NK cells play an important role in fighting off viral infections. In initial patients with severe cases of COVID-19, low NK cell counts were observed.

The NK cells used in this study are derived from blood stem cells obtained from the placenta. They will be administered to patients diagnosed with a COVID-19 infection causing pneumonia.

In a press release, IDRI’s CEO Corey Casper talks in more detail about how the NK cells could help treat patients with COVID-19.

“The hypothesis is that administering NK cells to patients with moderate to severe COVID-19 will allow the immune cells find the sites of active viral infection, kill the virus, and induce a robust immune response that will help heal the damage and control the infection.”

In the same press release, Corey Casper also mentions the other applications this treatment could have.

“Beyond its promise as a critically needed treatment for COVID-19, the biology of NK cells indicates a possibility that this immunotherapy could be used as an off-the-shelf treatment for future pandemic infections.”