How two California researchers are advancing world class science to develop real life solutions

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In our recently launched 5-year Strategic Plan, the California Institute for Regenerative Medicine (CIRM) profiled two researchers who have leveraged CIRM funding to translate basic biological discoveries into potential real-world solutions for devastating diseases.

Dr. Joseph Wu is director of the Stanford Cardiovascular Institute and the recipient of several CIRM awards. Eleven of them to be exact! Over the past 10 years, Dr. Wu’s lab has extensively studied the application of induced pluripotent stem cells (iPSCs) for cardiovascular disease modeling, drug discovery, and regenerative medicine. 

Dr. Wu’s extensive studies and findings have even led to a cancer vaccine technology that is now being developed by Khloris Biosciences, a biotechnology company spun out by his lab. 

Through CIRM funding, Dr. Wu has developed a process to produce cardiomyocytes (cardiac muscle cells) derived from human embryonic stem cells for clinical use and in partnership with the agency. Dr. Wu is also the principal investigator in the first-in-US clinical trial for treating ischemic heart disease. His other CIRM-funded work has also led to the development of cardiomyocytes derived from human induced pluripotent stem cells for potential use as a patch.

Over at UCLA, Dr. Lili Yang and her lab team have generated invariant Natural Killer T cells (iNKT), a special kind of immune system cell with unique features that can more effectively attack tumor cells. 

More recently, using stem cells from donor cord-blood and peripheral blood samples, Dr. Yang and her team of researchers were able to produce up to 300,000 doses of hematopoietic stem cell-engineered iNKT (HSC–iNKT) cells. The hope is that this new therapy could dramatically reduce the cost of producing immune cell products in the future. 

Additionally, Dr. Yang and her team have used iNKT cells to develop both autologous (using the patient’s own cells), and off-the-shelf anti-cancer therapeutics (using donor cells), designed to target blood cell cancers.

The success of her work has led to the creation of a start-up company called Appia Bio. In collaboration with Kite Pharma, Appia Bio is planning on developing and commercializing the promising technology. 

CIRM has been an avid supporter of Dr. Yang and Dr. Wu’s research because they pave the way for development of next-generation therapies. Through our new Strategic Plan, CIRM will continue to fund innovative research like theirs to accelerate world class science to deliver transformative regenerative medicine treatments in an equitable manner to a diverse California and the world.

Visit this page to learn more about CIRM’s new 5-year Strategic Plan and stay tuned as we share updates on our 5-year goals here on The Stem Cellar.

How some brilliant research may have uncovered a potential therapy for Alzheimer’s 

Dr. Nicole Koutsodendris, photo courtesy Gladstone Institutes

In the world of scientific research, the people doing clinical trials tend to suck up all the oxygen in the room. They’re the stars, the ones who are bringing potential therapies to patients. However, there’s another group of researchers who toil away in the background, but who are equally deserving of praise and gratitude. 

Dr. Lana Zholudeva, photo courtesy Gladstone Institutes

These are the scientists who do basic or discovery-level research. This is where all great therapies start. This is where a researcher gets an idea and tests it to see if it holds promise. A good idea and a scientist who asks a simple question, “I wonder if…..”  

Dr. Yadong Huang, Photo courtesy Gladstone Institutes

In our latest “Talking ‘Bout (re)Generation” podcast we talk to three researchers who are asking those questions and getting some truly encouraging answers. They are scientists at the Gladstone Institutes in San Francisco: one seasoned scientist and two young post-docs trying to make a name for themselves. And they might just have discovered a therapy that could help people battling Alzheimer’s disease. 

Enjoy the podcast.


  

Lack of diversity impacts research into Alzheimer’s and dementia

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A National Institutes of Allergy and Infectious Diseases clinical trial admissions coordinator collects information from a volunteer to create a medical record. Credit: NIAID

Alzheimer’s research has been in the news a lot lately, and not for the right reasons. The controversial decision by the Food and Drug Administration (FDA) to approve the drug Aduhelm left many people wondering how, when, or even if it should be used on people battling Alzheimer’s disease. Now a new study is raising questions about many of the clinical trials used to test medications like Aduhelm.

The research, published in the journal Jama Neurology, looked at 302 studies on dementia published in 2018 and 2019. Most of these studies were carried out in North America or Europe, and almost 90 percent of those studied were white.

In an accompanying editorial in the journal, Dr. Cerise Elliott, PhD, of the National Institute on Aging (NIA) in Bethesda, Maryland, and co-authors wrote that this limited the value of the studies: “This, combined with the fact that only 22% of the studies they analyzed even reported on race and ethnicity, and of those, a median 89% of participants were white, reflects the fact that recruitment for research participation is challenging; however, it is unacceptable that studies continue to fail to report participant demographics and that publishers allow such omissions.”

That bias is made all the more glaring by the fact that recent data from the Centers for Disease Control and Prevention shows that among people 65 and older, the Black community has the highest prevalence of Alzheimer’s disease and related dementias (13.8%), followed by Latinx (12.2%), non-Hispanic white (10.3%), American Indian and Alaskan Native (9.1%), and Asian and Pacific Islander (8.4%) populations.

The researchers admitted that the limited sample size – more than 40 percent of the studies they looked at included fewer than 50 patients – could have impacted their findings. Even so this clearly suggests there is a huge divide between the people at greatest risk of developing Alzheimer’s, or some other form of dementia, and the people being studied.

In the editorial, Elliott and his colleagues wrote that without a more diverse and balanced patient population this kind of research: “will continue to underrepresent people most affected by the disease and perpetuate systems that exclude important valuable knowledge about the disease.”


There are more details on this in Medpage Today.

An editorial in the New England Journal of Medicine highlights how this kind of bias is all too common in medical research.

“For years, the Journal has published studies that simply do not include enough participants from the racial and ethnic groups that are disproportionately affected by the illnesses being studied to support any conclusions about their treatment. In the United States, for example, Black Americans have high rates of hypertension and chronic kidney disease, Hispanic Americans have the highest prevalence of nonalcoholic fatty liver disease, Native Americans are disproportionately likely to have metabolic syndrome, and Asian Americans are at particular risk for hepatitis B infection and subsequent cirrhosis, but these groups are frequently underrepresented in clinical trials and cohort studies.”

“For too long, we have tolerated conditions that actively exclude groups from critical resources in health care delivery, research, and education. This exclusion has tragic consequences and undermines confidence in the institutions and the people who are conducting biomedical research. And clinicians cannot know how to optimally prevent and treat disease in members of communities that have not been studied.”

The encouraging news is that, finally, people are recognizing the problem and trying to come up with ways to correct it. The not so encouraging is that it took a pandemic to get us to pay attention.

At CIRM we are committed to being part of the solution. We are now requiring everyone who applies to us for funding to have a written plan on Diversity, Equity and Inclusion, laying out how their work will reflect the diversity of California. We know this will be challenging for all of us. But the alternative, doing nothing, is no longer acceptable.

Stem cell therapy may help mend a broken heart

Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014

Dilated cardiomyopathy (DCM), a condition where the muscles of the heart are weak and can lead to heart failure, is considered rare in children. However, because the symptoms are not always easy to recognize the condition can go unnoticed for many years, and in severe cases can damage the heart irreparably. In that case the child’s only option is a heart transplant, and a lack of organ donors means that is not always available.

Now, new research out of Japan – published in the journal Science Translation Medicine – could lead the way to new treatments to help children avoid the need for a transplant.

In the study, researchers at Okayama University used heart stem cells called cardiosphere-derived cells (CDCs) to try and repair the damage caused by DCM.  

In a news release, lead researcher Professor Hidemasa Oh, says previous work has shown that because CDCs have the ability to turn into heart tissue they have the potential of reversing damage, but it’s not clear if this would work in children.

“I have been working on cardiac regeneration therapy since 2001. In this study, my team and I assessed the safety and efficacy of using CDCs to treat DCM in children.”

Tests in animal models with DCM showed that the CDCs resulted in a thickening of the heart muscle leading to increased blood flow around the body. This increased blood supply helped repair damaged tissue. Based on this trial the researcher determined what might be a suitable dose of CDCs for children with DCM and were granted permission to carry out a Phase 1 clinical trial.

Five young patients were treated and the results were cautiously encouraging. After a year none of the patients had experienced any severe side effects, but all had indications of improved heart function.

The study also gave the researchers some strong clues as to how the therapy seem to work. They found that when the CDCs were transplanted into the patient they secreted exosomes, which play an important role in cells communicating with one another. These exosomes then helped create a series of actions within the body; they blocked further damage to the heart tissue and they also helped kickstart the repair process.

The Okayama team are now hoping to carry out a Phase 2 clinical trial with more patients. Ultimately, they hope to be able to see if this approach could help prevent the need for a heart transplant in children, and even adults.

CIRM funds clinical trials targeting heart disease, stroke and childhood brain tumors

Gary Steinberg (Jonathan Sprague)

Heart disease and stroke are two of the leading causes of death and disability and for people who have experienced either their treatment options are very limited. Current therapies focus on dealing with the immediate impact of the attack, but there is nothing to deal with the longer-term impact. The CIRM Board hopes to change that by funding promising work for both conditions.

Dr. Gary Steinberg and his team at Stanford were awarded almost $12 million to conduct a clinical trial to test a therapy for motor disabilities caused by chronic ischemic stroke.  While “clot busting” therapies can treat strokes in their acute phase, immediately after they occur, these treatments can only be given within a few hours of the initial injury.  There are no approved therapies to treat chronic stroke, the disabilities that remain in the months and years after the initial brain attack.

Dr. Steinberg will use embryonic stem cells that have been turned into neural stem cells (NSCs), a kind of stem cell that can form different cell types found in the brain.  In a surgical procedure, the team will inject the NSCs directly into the brains of chronic stroke patients.  While the ultimate goal of the therapy is to restore loss of movement in patients, this is just the first step in clinical trials for the therapy.  This first-in-human trial will evaluate the therapy for safety and feasibility and look for signs that it is helping patients.

Another Stanford researcher, Dr. Crystal Mackall, was also awarded almost $12 million to conduct a clinical trial to test a treatment for children and young adults with glioma, a devastating, aggressive brain tumor that occurs primarily in children and young adults and originates in the brain.  Such tumors are uniformly fatal and are the leading cause of childhood brain tumor-related death. Radiation therapy is a current treatment option, but it only extends survival by a few months.

Dr. Crystal Mackall and her team will modify a patient’s own T cells, an immune system cell that can destroy foreign or abnormal cells.  The T cells will be modified with a protein called chimeric antigen receptor (CAR), which will give the newly created CAR-T cells the ability to identify and destroy the brain tumor cells.  The CAR-T cells will be re-introduced back into patients and the therapy will be evaluated for safety and efficacy.

Joseph Wu Stanford

Stanford made it three in a row with the award of almost $7 million to Dr. Joe Wu to test a therapy for left-sided heart failure resulting from a heart attack.  The major issue with this disease is that after a large number of heart muscle cells are killed or damaged by a heart attack, the adult heart has little ability to repair or replace these cells.  Thus, rather than being able to replenish its supply of muscle cells, the heart forms a scar that can ultimately cause it to fail.  

Dr. Wu will use human embryonic stem cells (hESCs) to generate cardiomyocytes (CM), a type of cell that makes up the heart muscle.  The newly created hESC-CMs will then be administered to patients at the site of the heart muscle damage in a first-in-human trial.  This initial trial will evaluate the safety and feasibility of the therapy, and the effect upon heart function will also be examined.  The ultimate aim of this approach is to improve heart function for patients suffering from heart failure.

“We are pleased to add these clinical trials to CIRM’s portfolio,” says Maria T. Millan, M.D., President and CEO of CIRM.  “Because of the reauthorization of CIRM under Proposition 14, we have now directly funded 75 clinical trials.  The three grants approved bring forward regenerative medicine clinical trials for brain tumors, stroke, and heart failure, debilitating and fatal conditions where there are currently no definitive therapies or cures.”

A new way to evade immune rejection in transplanting cells

Immune fluorescence of HIP cardiomyocytes in a dish; Photo courtesy of UCSF

Transplanting cells or an entire organ from one person to another can be lifesaving but it comes with a cost. To avoid the recipient’s body rejecting the cells or organ the patient has to be given powerful immunosuppressive medications. Those medications weaken the immune system and increase the risk of infections. But now a team at the University of California San Francisco (UCSF) have used a new kind of stem cell to find a way around that problem.

The cells are called HIP cells and they are a specially engineered form of induced pluripotent stem cell (iPSC). Those are cells that can be turned into any kind of cell in the body. These have been gene edited to make them a kind of “universal stem cell” meaning they are not recognized by the immune system and so won’t be rejected by the body.

The UCSF team tested these cells by transplanting them into three different kinds of mice that had a major disease; peripheral artery disease; chronic obstructive pulmonary disease; and heart failure.

The results, published in the journal Proceedings of the National Academy of Science, showed that the cells could help reduce the incidence of peripheral artery disease in the mice’s back legs, prevent the development of a specific form of lung disease, and reduce the risk of heart failure after a heart attack.

In a news release, Dr. Tobias Deuse, the first author of the study, says this has great potential for people. “We showed that immune-engineered HIP cells reliably evade immune rejection in mice with different tissue types, a situation similar to the transplantation between unrelated human individuals. This immune evasion was maintained in diseased tissue and tissue with poor blood supply without the use of any immunosuppressive drugs.”

Deuse says if this does work in people it may not only be of great medical value, it may also come with a decent price tag, which could be particularly important for diseases that affect millions worldwide.

“In order for a therapeutic to have a broad impact, it needs to be affordable. That’s why we focus so much on immune-engineering and the development of universal cells. Once the costs come down, the access for all patients in need increases.”

Two voices, one message, watch out for predatory stem cell clinics

Last week two new papers came out echoing each other about the dangers of bogus “therapies” being offered by predatory stem cell clinics and the risks they pose to patients.

The first was from the Pew Charitable Trusts entitled: ‘Harms Linked to Unapproved Stem Cell Interventions Highlight Need for Greater FDA Enforcement’ with a subtitle: Unproven regenerative medical products have led to infections, disabilities, and deaths.’

That pretty much says everything you need to know about the report, and in pretty stark terms; need for greater FDA enforcement and infections, disabilities and deaths.

Just two days later, as if in response to the call for greater enforcement, the Food and Drug Administration (FDA) came out with its own paper titled: ‘Important Patient and Consumer Information About Regenerative Medicine Therapies.’ Like the Pew report the FDA’s paper highlighted the dangers of unproven and unapproved “therapies” saying it “has received reports of blindness, tumor formation, infections, and more… due to the use of these unapproved products.”

The FDA runs down a list of diseases and conditions that predatory clinics claim they can cure without any evidence that what they offer is even safe, let alone effective. It says Regenerative Medicine therapies have not been approved for the treatment of:

  • Arthritis, osteoarthritis, rheumatism, hip pain, knee pain or shoulder pain.
  • Blindness or vision loss, autism, chronic pain or fatigue.
  • Neurological conditions like Alzheimer’s and Parkinson’s.
  • Heart disease, lung disease or stroke.

The FDA says it has warned clinics offering these “therapies” to stop or face the risk of legal action, and it warns consumers: “Please know that if you are being charged for these products or offered these products outside of a clinical trial, you are likely being deceived and offered a product illegally.”

It tells consumers if you are offered one of these therapies – often at great personal cost running into the thousands, even tens of thousands of dollars – you should contact the FDA at ocod@fda.hhs.gov.

The Pew report highlights just how dangerous these “therapies” are for patients. They did a deep dive into health records and found that between 2004 and September 2020 there were more than 360 reported cases of patients experiencing serious side effects from a clinic that offered unproven and unapproved stem cell procedures.

Those side effects include 20 deaths as well as serious and even lifelong disabilities such as:

  • Partial or complete blindness (9).
  • Paraplegia (1).
  • Pulmonary embolism (6).
  • Heart attack (5).
  • Tumors, lesions, or other growths (16).
  • Organ damage or failure in several cases that resulted in death.

More than one hundred of the patients identified had to be hospitalized.

The most common type of procedures these patients were given were stem cells taken from their own body and then injected into their eye, spine, hip, shoulder, or knee. The second most common was stem cells from a donor that were then injected.

The Pew report cites the case of one California-based stem cell company that sold products manufactured without proper safety measures, “including a failure to properly screen for communicable diseases such as HIV and hepatitis B and C.” Those products led to at least 13 people being hospitalized due to serious bacterial infection in Texas, Arizona, Kansas, and Florida.

Shocking as these statistics are, the report says this is probably a gross under count of actual harm caused by the bogus clinics. It says the clinics themselves rarely report adverse events and many patients don’t report them either, unless they are so serious that they require medical intervention.

The Pew report concludes by saying the FDA needs more resources so it can more effectively act against these clinics and shut them down when necessary. It says the agency needs to encourage doctors and patients to report any unexpected side effects, saying: “devising effective strategies to collect more real-world evidence of harm can help the agency in its efforts to curb the growth of this unregulated market and ensure that the regenerative medicine field develops into one that clinicians and patients can trust and safely access.”

We completely support both reports and will continue to work with the FDA and anyone else opposed to these predatory clinics. You can read more here about what we have been doing to oppose these clinics, and here is information that will help inform your decision if you are thinking about taking part in a stem cell clinical trial but are not sure if it’s a legitimate one.

How stem cells play “follow the leader”

Todd McDevitt, PhD., Photo: courtesy Gladstone Institutes

It’s hard enough trying to follow the movements of individuals in a crowd of people but imagine how much harder it is to follow the movements of stem cells, crowded into a tiny petri dish. Well, researchers at the Gladstone Institutes in San Francisco have done just that.

In a CIRM-funded study ($5.85M) Dr. Todd McDevitt and his team created a super smart artificial intelligence way of tracking the movements of hundreds of stem cells growing together in a colony, and even identify “leaders” in the pack.

In our bodies groups of stem cells are able to move in specific ways to form different organs and tissues when exposed to the right environment. Unfortunately, we are still trying to learn what “the right environment” is for different organs.

In a news release, McDevitt, the senior author of the paper published in the journal Stem Cell Reports, says this method of observing cells may help us better understand that.

“If I wanted to make a new human heart right now, I know what types of cells are needed, and I know how to grow them independently in dishes. But we really don’t know how to get those cells to come together to form something as complex as a heart. To accomplish that, we need more insights into how cells work cooperatively to arrange themselves.”

Normally scientists watch cells by tagging them with a fluorescent marker so they can see them under a microscope. But this is slow, painstaking work and not particularly accurate. This new method used a series of what are called “neural networks”, which are artificial intelligence (AI) programs that can detect patterns in the movements of the cells. When combined together the networks proved to be able to track the movement of 95 percent of the cells. Humans by comparison can only manage up to 90 percent. But the nets were not only sharper, they were also faster, much faster, some 500 times faster.

This enhanced ability to watch the cells showed that instead of being static most of the time, as had previously been thought, they were actually on the move a lot of the time. They would move around for 15 minutes and then take a breather for ten minutes (time for the stem cell equivalent of a cup of tea perhaps).  

Some cells moved around a lot in one direction, while others just seemed to shuffle around in the same area. Some cells even seemed to act as “leaders” while other cells appeared to be “followers” and shuffle along behind them.

None of this would have been visible without the power of the AI networks and McDevitt says being able to tap into this could help researchers better understand how to use these complex movements.

“This technique gives us a much more comprehensive view of how cells behave, how they work cooperatively, and how they come together in physical space to form complex organs.

Follow the Leader is not just a kids’ game anymore. Now it’s a scientific undertaking.

Persistence pays off in search for clue to heart defects

A team of scientists led by Benoit Bruneau (left), including Irfan Kathiriya (center) and Kavitha Rao (right), make inroads into understanding what genes are improperly deployed in some cases of congenital heart disease.  Photo courtesy Gladstone Institute

For more than 20 years Dr. Benoit Bruneau has been trying to identify the causes of congenital heart disease, the most common form of birth defect in the U.S. It turns out that it’s not one cause, but many.

Congenital heart disease covers a broad range of defects, some relatively minor and others life-threatening and even fatal. It’s been known that a mutation in a gene called TBX5 is responsible for some of these defects, so, in a CIRM-funded study ($1.56 million), Bruneau zeroed in on this mutation to see if it could help provide some answers.

In the past Bruneau, the director of the Gladstone Institute of Cardiovascular Disease, had worked with a mouse model of TBX5, but this time he used human induced pluripotent stem cells (iPSCs). These are cells that can be manipulated in the lab to become any kind of cell in the human body. In a news release Bruneau says this was an important step forward.

“This is really the first time we’ve been able to study this genetic mutation in a human context. The mouse heart is a good proxy for the human heart, but it’s not exactly the same, so it’s important to be able to carry out these experiments in human cells.”

The team took some iPSCs, changed them into heart cells, and used a gene editing tool called CRISPR-Cas9 to create the kinds of mutations in TBX5 that are seen in people with congenital heart disease. What they found was some genes were affected a lot, some not so much. Which is what you might expect in a condition that causes so many different forms of problems.

“It makes sense that some are more affected than others, but this is the first experimental data in human cells to show that diversity,” says Bruneau.

But they didn’t stop there. Oh no. Then they did a deep dive analysis to understand how the different ways that different cells were impacted related to each other. They found some cells were directly affected by the TBX5 mutation but others were indirectly affected.

The study doesn’t point to a simple way of treating congenital heart disease but Bruneau says it does give us a much better understanding of what’s going wrong, and perhaps will give us better ideas on how to stop that.

“Our new data reveal that the genes are really all part of one network—complex but singular—which needs to stay balanced during heart development. That means if we can figure out a balancing factor that keeps this network functioning, we might be able to help prevent congenital heart defects.”

The study is published in the journal Developmental Cell.

CIRM-funded study discovers potential therapy for one of the leading causes of heart disease

Dr. Deepak Srivastava and his team found a drug candidate that could help prevent tens of thousands of heart surgeries every year. Image Credit: Gladstones Institute

According to the Center for Disease Control and Prevention (CDC), heart disease is the leading cause of death for men, women, and people of most racial and ethnic groups in the United States. About 655,000 Americans die from heart disease each year, which is about one in every four deaths.

Calcific aortic valve disease, the third leading cause of heart disease overall, occurs when calcium starts to accumulate in the heart valves and vessels over time, causing them to gradually harden like bone. This leads to obstruction of blood flow out of the heart’s pumping chamber, causing heart failure. Unfortunately there is no treatment for this condition, leaving patients only with the option of surgery to replace the heart valve once the hardening is severe enough.

But thanks to a CIRM-funded ($2.4 million) study conducted by Dr. Deepak Srivastava and his team at the Gladstone Institutes, a potential drug candidate for heart valve disease was discovered. It has been found to function in both human cells and animals and is ready to move toward a clinical trial.

For this study, Dr. Srivastava and his team looked for drug-like molecules that had the potential to correct the mechanism in heart valve disease that leads to gradual hardening. To do so, the team first had to determine the network of genes that are turned on or off in the diseased cells.

Once the genes were identified, they used an artificial intelligence method to train a machine learning program to detect whether a cell was healthy or diseased based on the network of genes identified. They proceeded to treat the diseased human cells with nearly 1,600 molecules in order to identify any drugs that would cause the machine learning program to reclassify diseased cells as healthy. The team successfully identified a few molecules that could correct diseased cells back to a healthy state.

Dr. Srivastara then collaborated with Dr. Anna Malashicheva, from the Russian Academy of Sciences, who had collected valve cells from over 20 patients at the time of surgical replacement. Using the valve cells that Dr. Malashicheva had collected, Dr. Srivastara and his team conducted a “clinical trial in a dish” in which they tested the molecules they had previously identified in the cells from the 20 patients with aortic valve hardening. The results were remarkable, as the molecule that seemed most effective in the initial study was able to restore these patients’ cells as well.

The final step taken was to determine whether the drug-like molecule would actually work in a whole, living organ. To do this, Dr. Srivastava and his team did a “pre-clinical trial” in a mouse model of the disease. The team found that the therapeutic candidate could successfully prevent and treat aortic valve disease. In young mice who had not yet developed the disease, the therapy prevented the hardening of the valve. In mice that already had the disease, the therapy was able to halt the disease and, in some cases, reverse it. This finding is especially important since most patients aren’t diagnosed until hardening of the heart valve has already begun.

Dr. Deepak Srivastava (left) and Dr. Christina V. Theodoris (right)
Image Credit: Gladstones Institute

Dr. Christina V. Theodoris, a lead author of the study who is now completing her residency in pediatric genetics, was a graduate student in Dr. Srivastava’s lab and played a critical role in this research. Her first project was to convert the cells from patient families into induced pluripotent stem cells (iPSCs), which have the potential of becoming any cell in the body. The newly created iPSCs were then turned into cells that line the valve, allowing the team to understand why the disease occurs. Her second project was to make a mouse model of calcific aortic valve disease, which enabled them to start using the models to identify a therapy.

In a press release from Gladstone Institutes, Dr. Theodoris, discusses the impact of the team’s research.

“Our strategy to identify gene network–correcting therapies that treat the core disease mechanism may represent a compelling path for drug discovery in a range of other human diseases. Many therapeutics found in the lab don’t translate well to humans or focus only on a specific symptom. We hope our approach can offer a new direction that could increase the likelihood of candidate therapies being effective in patients.”

In the same press release, Dr. Srivastava emphasizes the scientific advances that have driven the team’s research to this critical point.

“Our study is a really good example of how modern technologies are facilitating the kinds of discoveries that are possible today, but weren’t not so long ago. Using human iPSCs and gene editing allowed us to create a large number of cells that are relevant to the disease process, while powerful machine learning algorithms helped us identify, in a non-biased fashion, the important genes for distinguishing between healthy and diseased cells.”

The full results of this study were published in Science.